Methods and devices for occlusion of an atrial appendage

ABSTRACT

Some embodiments of the invention provide a system for occluding a left atrial appendage of a patient. Some embodiments of the system can include a ring occluder that can be positioned around the left atrial appendage and a ring applicator to position the ring occluder with respect to the left atrial appendage. One embodiment discloses a method of accessing endocardial surfaces of the heart through the atrial appendage. Additional embodiments of the invention provide a clip occluder that can be positioned around the left atrial appendage. A clip applicator can position the clip occluder with respect to the left atrial appendage.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.11/155,699 filed Jun. 17, 2005, which claims the benefit of U.S.Application Ser. Nos. 60/581,223 filed on Jun. 18, 2004, and 60/685,681filed on May 27, 2005, all of which are incorporated herein by referencein their entirety. This application also claims the benefit of U.S.Application Ser. No. 60/795,752 filed Apr. 28, 2006, the disclosure ofwhich is also incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to methods and devices for occlusion or ligationof an atrial appendage.

BACKGROUND OF THE INVENTION

Embolic stroke is the nation's third leading killer for adults. Embolicstroke is also a major cause of disability. The most common cause ofembolic stroke is thrombus formation in the left appendage on theatrium. In almost all atrial fibrillation (AF) patients suffering fromembolic stroke, a thrombus clot forms in the appendage of the leftatrium.

The primary therapy for the prevention of stroke in AF patients is theadministration of oral anticoagulants. Although somewhat effective,there are numerous side effects, including bleeding and lifestylecompromises. Pharmacological therapies (such as Warfarin®) are not welltolerated by patients. The introduction of biomaterials into the leftatrial appendage has resulted in the biomaterials eventually breakingdown resulting in clot formation. The left atrial appendage has beenremoved by others via open chest and thoroscopic surgical approaches.Such a procedure is described by Johnson in U.S. Pat. No. 5,306,234entitled “Method for Closing an Atrial Appendage.” The '234 patentdiscloses a method for grasping the left atrial appendage andmanipulating it into position in order to sever the tissue and removethe appendage. The wound on the heart is then sewn or clamped shut.

Appriva Medical, Inc. disclosed concepts for occluding the left atrialappendage from a percutaneous endocardial approach. In U.S. Pat. No.6,152,144 entitled “Method and Device for Left Atrial AppendageOcclusion” assigned to Appriva Medical, a device and method forisolating the left atrial appendage from the inside of the heart isdisclosed. A barrier or other device is anchored in the chamber of theleft atrial appendage to prevent the passage of blood into and out ofthe chamber and thereby prevent clot formation. However, any foreigndevice left in the chamber of the heart is a potentialthrombosis-generating site. In addition, biomaterials are known toeventually break down and result in clotting.

Some surgeons will remove or oversew the left atrial appendage as aconcomitant procedure during other cardiac surgery. This is done undergeneral anesthesia and may result in additional trauma to the patient.

While endoscopic or percutaneous approaches reduce the invasiveness ofthe surgical procedure, the above-described approaches have inherentlimitations. Surgical removal of the left atrial appendage is veryinvasive and often results in loss of atrial hormones, such as atrialnatriuretic peptide (ANP), and significant bleeding. In U.S. Pat. No.6,666,861 issued to Grabek and entitled “Atrial Remodeling Device andMethod,” a method is disclosed for applying a suture lasso placedendoscopically around the left atrial appendage to isolate it from theatrium. The '861 patent describes using either wet cauterization toremove the tissue or leaving the isolated appendage in place.

Endoscopic stapling devices, suture loops tied to the base of theappendage, and clips pinching the appendage from the outside surface tothe base to close the appendage are used by physicians to isolate andremove the left atrial appendage. In U.S. Pat. No. 6,488,689 issued toKaplan and entitled “Methods and Apparatus for Transpericardial LeftAtrial Appendage Closure,” a method and apparatus to close the leftatrial appendage is disclosed. The '689 patent describes using a grasperand a closing loop or clip applied to the outside of the left atrialappendage. The clip is applied extending toward the chamber of theatrial appendage and extending over the outside edge of the appendage.The clips of the '689 patent are a U-shaped metal clip, having a springtendency to hold its shape, being deformed to open while positioned toextend over the tissue, before the clip is allowed to return to itsresting shape, having the tissue pinched between the ends of the clip.

SUMMARY OF THE INVENTION

Some embodiments of the invention provide a system for occluding a leftatrial appendage of a patient. Some embodiments of the system caninclude a ring occluder that can be positioned around the left atrialappendage and a ring applicator to position the ring occluder withrespect to the left atrial appendage. The ring applicator can include aring spreader with a spreader hinge coupled to an upper spreader jaw anda lower spreader jaw. The ring occluder can be coupled between the lowerspreader jaw and the upper spreader jaw. The spreader hinge can movebetween an open position in which the ring occluder has a first diameterand a closed position in which the ring occluder has a second diameter,the first diameter being larger than the second diameter.

Other embodiments of the invention provide a clip occluder that can bepositioned around the left atrial appendage. The clip occluder caninclude a clip hinge coupled to an upper clip jaw and a lower clip jaw.The clip occluder can include a clip lock. A clip applicator canposition the clip occluder with respect to the left atrial appendage.The clip applicator can include a clip actuator coupled to the clipoccluder by an actuator suture. The actuator suture can control adistance between the upper clip jaw and the lower clip jaw. The clipapplicator can be removably coupled to the clip occluder with aretention suture.

In some embodiments of the invention, a ring applicator can include ashaft having a handle on a proximal end and a distal end, and a lumen orchannel extending from the handle to the distal end of the shaft, anactuator coupled to the handle, and a ring spreader assembly on thedistal end of the shaft. In one embodiment, the ring spreader assemblymay include a plurality of ring expanding members. In an alternativeembodiment, the ring spreader assembly may include a spreader drivewire. A ring occluder may be releasably attached to the plurality ofring expanding members or to the drive wire. The ring occluder can bestretched to an open position by the actuator which is coupled to thering expanding members or the drive wire to allow the ring occluder tobe manipulated over tissue to be occluded.

In some embodiments of the invention, the occluder member, e.g., a ringoccluder or clip occluder, may comprise one or more pharmacologicaland/or biological agents, e.g., anti-inflammatory and/or anti-arrhythmicagents and/or drugs. In some embodiments, the occluder member mayinclude a fabric covering.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a left atrial appendage occlusiondevice according to one embodiment of the invention placed around theleft atrium before compressing the tissue of the left atrial appendage.

FIG. 2 is a schematic illustration of the left atrial appendageocclusion device of FIG. 1 clamped around the left atrial appendage.

FIG. 3 is a perspective view of a ring occluder on a patient's heartisolating the left atrial appendage.

FIG. 4 is a perspective view of a variety of ring occluders illustratingthe relative size differences that are available.

FIG. 5 is a perspective view of a ring occluder applicator according toone embodiment of the invention.

FIG. 6 is a perspective view of an applicator head of the ring occluderapplicator of FIG. 5.

FIG. 7 is a perspective view of the handle mechanism of the ringoccluder applicator of FIG. 5.

FIG. 7A is a perspective view of the ring occluder applicator in FIG. 5with a ring occluder attached.

FIG. 8 is a perspective view of the ring occluder applicator of FIG. 5with a ring occluder attached and in a stretched-open position.

FIG. 9A is a side view of the ring occluder applicator of FIG. 7 withthe ring occluder in a relaxed position.

FIG. 9B is a side view of the ring occluder applicator in FIG. 7 withthe ring occluder in a partially-stretched open position.

FIG. 9C is a side view of the ring occluder applicator of FIG. 7 withthe ring occluder in a stretched-open position.

FIG. 10 is a cross-sectional schematic illustration of a left atrialappendage occlusion device according to one embodiment of the invention,before being clamped around the left atrial appendage.

FIG. 11 is a cross-sectional schematic illustration of the occlusiondevice of FIG. 10, after being clamped around the left atrial appendage.

FIG. 12 is a perspective view of the occlusion device of FIG. 10 appliedto a patent's heart.

FIG. 12A is an end view of the occlusion device of FIG. 10 applied to apatient's heart.

FIG. 13 is a perspective view of a clip applicator according to oneembodiment of the invention.

FIG. 14 is a perspective view of an applicator head of the clipapplicator of FIG. 13.

FIG. 15 is a perspective view of the clip applicator of FIG. 14 with theclip attached and in a spring-biased open position.

FIG. 16 is a perspective view of the clip applicator of FIG. 14 with theclip attached and in an insert position.

FIG. 17 is a perspective view of the clip applicator of FIG. 14 with theclip detached and in a locked position.

FIG. 18 is a cross-sectional schematic illustration of a left atrialappendage occlusion device according to one embodiment of the invention,before compressing tissue of the left atrial appendage.

FIG. 19 is a cross-sectional schematic illustration of the occlusiondevice of FIG. 18, after being clamped around the left atrial appendage.

FIG. 20 is a cross-sectional schematic illustration of the occlusiondevice of FIG. 20 with one or more ratcheting arms removed.

FIG. 21 is a cross-sectional schematic illustration of a left atrialappendage occlusion device according to one embodiment of the invention,before compressing tissue of the left atrial appendage.

FIG. 22 is a cross-sectional schematic illustration of the occlusiondevice FIG. 22 after compressing tissue of the left atrial appendage.

FIG. 23 is a perspective view of an applicator for inserting andapplying a left atrial appendage occluder according to one embodiment ofthe invention.

FIG. 24 is an exploded perspective view of the occluder of FIG. 23.

FIG. 25 is a perspective view of the occluder of FIG. 24 after assembly.

FIG. 26 is a perspective view of the occluder of FIG. 25 being mountedon the applicator of FIG. 23.

FIG. 27 is a perspective view of the occluder fully mounted on theapplicator of FIG. 23.

FIG. 28 is a perspective view of the occluder compressed on theapplicator of FIG. 23.

FIG. 29 is a perspective view of the occluder compressed anddisconnected from the applicator of FIG. 23.

FIG. 30 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 31 is a partial perspective view of the device of FIG. 30 in use.

FIG. 32 is a schematic illustration of an occlusion device according toone embodiment of the invention positioned around the left atrialappendage.

FIG. 33 is a schematic illustration of the occlusion device of FIG. 32clamped around the left atrial appendage.

FIG. 34 is a perspective view of an adjustable band occluder accordingto one embodiment of the invention.

FIG. 35 is a perspective view of a deployed percutaneous left atrialappendage transcatheter occlusion (PLAATO) device.

FIGS. 36A-E are perspective views of an endoloop left atrial appendageligation procedure.

FIGS. 37A-E are side and perspective views of an atrial septal defectrepair device.

FIG. 38 is a schematic cross-sectional representation of a heart and achest wall.

FIG. 39 is a side view of a device according to one embodiment of theinvention passed through a port placed between the ribs.

FIG. 40 is a side view of the device of FIG. 39 advanced toward the leftatrial appendage.

FIG. 41 is a side view of the device of FIG. 39 including a suction cupor grasper probe being advanced through portal tube.

FIG. 42 is a side view of the device of FIG. 41 with the suction cup orgrasper probe attached to an end of the left atrial appendage.

FIG. 43 is a side view the device of FIG. 41 with cinch-ring supportarms expanded and the left atrial appendage pulled toward a portal tube.

FIG. 44 is a side view of the device of FIG. 41 with the cinch-ringsupport arms advanced over the left atrial appendage.

FIG. 45 is a side view of the device of FIG. 41 with the cinch-ringsupport arms positioned over a mid to proximal left atrial appendage.

FIG. 46 is a side view of the device of FIG. 41 with the cinch-ringsupport arms allowed to contract over the left atrial appendage andocclude a lumen of the left atrial appendage.

FIG. 47 is a side view of the device of FIG. 41 with the suction cup orgrasper probe removed from the portal tube.

FIG. 48 is a side view of a dilator/sheath assembly advanced through theportal tube.

FIG. 49 is a side view of the dilator/sheath assembly of FIG. 48 with aneedle or sharp wire advanced through a lumen of the dilator to punctureinto the left atrial appendage lumen.

FIG. 50 is a side view of the dilator of FIG. 49 advanced into the lumenof left atrial appendage and the needle retracted.

FIG. 51 is a side view of the dilator of FIG. 49 with the sheathadvanced over the dilator into left atrial appendage lumen.

FIG. 52 is a side view of the dilator of FIG. 51 with the left atrialappendage lumen being aspirated of blood and flushed with heparinizedsaline to prevent thrombus formation.

FIG. 53 is a side view of the dilator of FIG. 51 with the left atrialappendage being filled with heparinized saline as blood and air areremoved.

FIG. 54 is a side view of the dilator of FIG. 51 being advanced past thecinch ring and into the left atrium.

FIG. 55 is a side view of the sheath of FIG. 51 being advanced over thedilator past the cinch ring and into the left atrium.

FIG. 56 is a side view of the sheath of FIG. 51 with the dilatorremoved.

FIG. 57 is a side view the sheath of FIG. 56 with therapeutic implementsbeing advanced into the left atrium.

FIG. 58 is a side view of a balloon ablation device according to oneembodiment of the invention at the right inferior pulmonary vein ostium.

FIG. 59 is a side view of the balloon ablation device of FIG. 58 at theleft superior pulmonary vein ostium.

FIG. 60 is a side view of an encircling ablation device according to oneembodiment of the invention approaching the left superior pulmonary veinostium.

FIG. 61 is a side view of the encircling ablation device of FIG. 60placed around the left superior pulmonary vein ostium.

FIG. 62 is a side view of a left atrial de-bulking spiral ablationdevice according to one embodiment of the invention placed against theposterior left atrium.

FIG. 63 is a side view of a high intensity focused ultrasound ablationdevice according to one embodiment of the invention creating a lesionover the left atrial isthmus.

FIG. 64 is a side view of a PFO or ASD closure device according to oneembodiment of the invention being deployed in the fossa ovalis of theinter-atrial septum.

FIG. 65 is a side view of a linear ablation device according to oneembodiment of the invention forming connecting lesions between pulmonaryveins.

FIG. 66 is a side view of an elastic cinch ring according to oneembodiment of the invention allowed to constrict down around the base ofthe left atrial appendage.

FIG. 67 is a side view of the elastic cinch ring of FIG. 66 immediatelyfollowing the procedure.

FIG. 68 is a side view of the elastic cinch ring of FIG. 66 afterapproximately 12 weeks.

FIG. 69 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 70 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 71 is a partial cross-sectional view of one embodiment of a deviceaccording to one embodiment of the invention.

FIG. 72 is a perspective view of one embodiment of a pair of devicesaccording to one embodiment of the invention.

FIG. 73 is a perspective view of one embodiment of a pair of devicesaccording to one embodiment of the invention.

FIG. 74 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 75 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 76 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 77 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 78 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 79 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 80 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 81 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 82 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 83 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 84 is a perspective view of a distal portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 85 is a perspective view of a portion of one embodiment of a deviceaccording to one embodiment of the invention.

FIG. 86 is a perspective view of a portion of one embodiment of a deviceaccording to one embodiment of the invention.

FIG. 87 is a perspective view of a portion of one embodiment of a deviceaccording to one embodiment of the invention.

FIG. 88 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 89 is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 90 is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 91 is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 92 is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 93 is a cross-sectional view of a portion of one embodiment of adevice according to one embodiment of the invention.

FIG. 94 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 95 is a cross-sectional view of one embodiment of a deviceaccording to one embodiment of the invention.

FIG. 96 is a perspective view of one embodiment of a device according toone embodiment of the invention.

FIG. 97 is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 98A is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 98B is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

FIG. 98C is a perspective view of a portion of a subassembly of oneembodiment of a device according to one embodiment of the invention.

DETAILED DESCRIPTION

FIG. 1 illustrates an outline of the atrium 10 of the heart with theleft atrial appendage 12 protruding therefrom. FIG. 1 also illustratesone embodiment of an occluder 14 forming a ring 16 that is placed in aposition to surround the left atrial appendage 12 adjacent to a leftatrial appendage base 18, where the left atrial appendage 12 is attachedto the heart 20. In some embodiments, the ring 16 can be constructed ofan elastic material to allow it to be stretched into an open position,as shown in FIG. 1. The ring 16 can be allowed to return to a closedposition, as shown in FIG. 2, to bear against the tissue of the leftatrial appendage 12 in order to close off any interior connectionbetween the atrium 10 and the left atrial appendage 12.

FIG. 3 illustrates the ring 16 attached to a patient's heart 20 toisolate the left atrial appendage 12 from the atrium 10. In someembodiments, the material of the ring 16 can be biocompatible to allowthe ring 16 to be left on the heart 20 permanently. Optionally, the ring16 may have tissue engaging surfaces for enhanced positionability and/ortissue engagement. The tissue engagement surfaces may comprise bumps,detents, grooves, ridges, ribs or the like. The ring 16 may also includebiocompatible coatings for any of the predetermined purposes disclosedherein. The biocompatible coatings may include a pharmacological agent(e.g. a controlled-release agent) for purposes of encouraging tissueingrowth, affording local apoptosis for therapeutic reasons, localnecrosis, revascularizationi, arrhythmia control, infection control,anti-bacterial, fluid balance (i.e. atrial natritic peptidereplacement), etc.

FIG. 4 illustrates different relative sizes of rings 16 that can be usedto accommodate different anatomy requirements of the patient. In oneembodiment, the ring 16 can be manufactured with radio opaque qualities,such as micro-sized glass beads 26 molded into the material of the ring16. Alternatively, the ring 16 can be made radio opaque by the additionof glass or metallic fibers 28 in the material of the ring 16. In someembodiments, the ring 16 can be entirely biocompatible to allow for usefor the life of the patient. The ring 16 can have size variations in itsinner diameter 30 along a contact surface 32. The ring 16 can also havedifferent cross-sectional shapes, such as oval, rectangular, square,etc.

To apply the ring 16 to a patient, a ring applicator 34, as shown inFIG. 5, can be used. In some embodiments, the ring applicator 34 caninclude a shaft 36 with a handle 38 on a proximal end and a ringspreader 40 on a distal end. The ring spreader 40 can include an upperspreader jaw 42 and a lower spreader jaw 44, each connected to aspreader hinge 46. A jaw actuator 48 on the handle 38 can include a knob50.

In some embodiments, the spreader hinge 46 can include a four-barassembly 52 for use in moving the upper spreader jaw 42 and the lowerspreader jaw 44 substantially in parallel. The four-bar assembly 52 caninclude a first distal link 54 and a second distal link 56, as shown inFIG. 6. The first distal link 54 can include a distal end pivotallyattached to the upper spreader jaw 42 at a top distal pivot 58. Thesecond distal link 56 can include a distal end pivotally attached to thelower spreader jaw 44 at a lower distal pivot 60. The first distal link54 can include a proximal end pivotally attached to the shaft 36 and toa proximal end of the second distal link 56 at a distal shaft pivot 57.As a result, the first distal link 54 can be pivotally linked to thesecond distal link 56.

The ring spreader 40 can be moved from a relaxed closed position (asshown in FIG. 9A) having the upper spreader jaw 42 in close proximity tothe lower spreader jaw 44 to an open position (as shown in FIGS. 8, 9B,and 9C) by the jaw actuator 48. In the open position, the upper spreaderjaw 42 can be spaced from the lower spreader jaw 44 by a larger distancethan in the closed position.

In some embodiments, as shown in FIG. 6, the ring 16 can be removablyattached to the ring spreader 40 by one or more sutures tied between thehandle 38 and the ring 16. In one embodiment, the ring 16 can be tied onthe front, back, top, and bottom to uniformly open the ring 16 forapplication to a tissue appendage. A front suture 66 and an upper suture68 can be attached to the jaw actuator 48 and can loop inside the shaft36 to the upper spreader jaw 42 and around the ring 16 at spacedintervals. A proximal suture 70 and a lower suture 72 can be similarlyattached to the jaw actuator 48 and can extend inside the shaft 36 tothe lower spreader jaw 44 and around the ring 16 at spaced intervals.

As shown in FIG. 6, the upper spreader jaw 42 can include a first feedslot 74 having a first distal aperture 75 extending through the upperjaw 42 and a first upper aperture 79 extending through the upper jaw 42.The first upper aperture 79 can be disposed between the first distalaperture 75 and the spreader hinge 46. The upper spreader jaw 42 caninclude a return slot 76 parallel to the first feed slot 74. The returnslot 76 can include a second distal aperture 77 in proximity to thefirst distal aperture 75 and a second upper aperture 81 in proximity tothe first upper aperture 79. In some embodiments, the first and secondupper apertures 79 and 81 can both extend through the upper jaw 42.

As shown in FIG. 7A, the lower spreader jaw 44 can include a similarconfiguration to the upper spreader jaw 42. The lower spreader jaw 44can include a second feed slot 65 with a first lower aperture 67 and afirst proximal aperture 69. The first proximal aperture 69 can bedisposed between the first lower aperture 67 and the spreader hinge 46.A second return slot 71 can be formed on the lower spreader jaw 44substantially parallel to the second feed slot 65. The second returnslot 71 can include a second lower aperture 73 in proximity to a firstlower aperture 67 and a second proximal aperture 53 in proximity to thefirst proximal aperture 69. The second proximal aperture 53 can bedisposed between the spreader hinge 46 and the second lower aperture 73.

The feed slots 65, 74 can be used to direct the sutures attached at thehandle 38 to the jaw actuator 48. The sutures 66, 68, 70, 72 can bedirected along the spreader jaws 42, 44 and directed to pass through thespreader jaws 42, 44 at the apertures 67, 69, 75, 79. The sutures can66, 68, 70, 72 then loop around the ring 16 at predefined locations. Thesutures 44, 42 can also pass through the apertures 53, 73, 79, 81 andalong the return slots 71, 76 to return through a lumen to attach to thejaw actuator 48. The front suture 66 can have a first end attached tothe jaw actuator 48. The front suture 66 can extend through the handle38, along the first feed slot 74, through the first distal aperture 75,and around the ring 16 in a single loop defining the front portion ofthe ring 16. The front suture 66 can also extend back through the seconddistal aperture 77, along the first return slot 76, and through thehandle 38 to a second end connected to the jaw actuator 48. Likewise,the upper suture 68 can extend through the handle 38, along the firstfeed slot 74, through the first upper aperture 79, and around the ring16 in a single loop defining the upper portion of the ring 16. The uppersuture 68 can also extend back through the second upper aperture 81,along the first return slot 76, and through the handle 38 to a secondend connected to the jaw actuator 48.

The lower suture 72 can have a first end attached to the jaw actuator48. The lower suture 72 can extend through the handle 38, along thesecond feed slot 65, through the first lower aperture 67, and around thering 16 in a single loop defining the lower portion of the ring 16. Thelower suture 72 can also extend back through the second lower aperture73, along the second return slot 71, and through the handle 38 to asecond end connected to the jaw actuator 48. Likewise, the proximalsuture 70 can extend through the handle 38, along the second feed slot65, through the first proximal aperture 69, and around the ring 16 in asingle loop defining the proximal portion of the ring 16. The proximalsuture 70 can also extend back through the second proximal aperture 53,along the second return slot 71, and through the handle 38 to a secondend connected to the jaw actuator 48.

FIG. 7 illustrates a torque screw 82 having a hex end 84 channeled inthe handle 38 and attached to the jaw actuator 48, according to oneembodiment of the invention. When the knob 50 is rotated, the torquescrew 82 can rotatably traverse to move the hex end 84 in the handle 38toward the ring spreader 40 or toward the knob 50, depending on whichdirection the knob 50 is rotated. The sutures 66, 68, 70, 72 can beattached to the hex end 84 using knots and can extend to loop around thering 16 in the ring spreader 40. As the knob 50 is turned to traversethe hex end 84 away from the ring spreader 40, the sutures 66, 68, 70,72 can tighten to bear against the ring 16 and the spreader jaws 42, 44in order to overcome the elasticity of the ring 16 and move the spreaderjaws 42, 44 to the open position, as shown in FIGS. 8 and 9C. Thespreader jaws 42, 44 can be guided in a substantially parallel path bythe four-bar assembly 52 in order to stretch the ring 16 to the openposition. In some embodiments, the hex end and the torque screw 82 arereplaced by a linear trigger grip. By squeezing the grip handle, thespreader jaws are spread as described above.

In some embodiments, as shown in FIGS. 9A-9C, the spreader hinge 46 caninclude a top proximal link 86 and a lower proximal link 88. The topproximal link 86 can include a first end pivotally attached to the shaft36 and a second end pivotally connected to the upper spreader jaw 42.The lower proximal link 88 can include a first end pivotally connectedto the shaft 36 and a second end pivotally connected to the lowerspreader jaw 44. The proximal links 86, 88 can function with the distallinks 54, 56 to move the upper spreader jaw 42 in a substantiallyparallel relationship with respect to the lower spreader jaw 44.

The sutures 66, 68, 70, 72 can act as a retainer to hold the ring 16 inthe ring spreader 40. The sutures 66, 68, 70, 72 can also act as aportion of the jaw actuator 48 by pulling the ring spreader 40 towardthe handle 38 to force the spreader hinge 46 to pivot at the four-barassembly 52, causing the spreader jaws 42, 44 to spread away from oneother and stretching the ring 16 open. The sutures 66, 68, 70, 72 canopen the ring 16 into a substantially rectangular shape as shown in FIG.9C.

As shown in FIG. 10, a left atrial appendage chamber 94 can bepositioned within a locking clip 96 in an open position. FIG. 11illustrates the chamber 94 compressed by the locking clip 96 in theclosed position. The locking clip 96 can include a lower clip jaw 118made of an elastic material and an upper clip jaw 124 connected to thelower clip law 118 at a clip hinge 122. In one embodiment, the lockingclip 96 can be formed from a single piece of elastic material 120 andcan define the clip hinge 122 integrally with the lower clip jaw 118 andupper clip jaw 124. The locking clip 96 can also include a clip lock 126(e.g., such as a clip barb 128) on the upper clip jaw 124, that isadapted to engage the lower clip jaw 118 at a lock receiver 130 tosubstantially permanently affix the upper clip jaw 124 to the lower clipjaw 118. FIGS. 12 and 12A illustrate an application of the locking clip96 on a patient's heart.

FIG. 13 illustrates one embodiment of a clip applicator 98 fordelivering a locking clip 96 into a patient through an incision in aclosed-chest routine. The clip applicator 98 can include a shaft 36having a handle 38 on a proximal end, a clip actuator 108 on the handle38, and a locking clip 96 coupled to a distal end.

The clip actuator 108 can be used to move the locking clip 96 from anopen, unlocked position to a closed, locked position. The clip actuator108 can include an actuator suture 110 having a first end attached tothe handle 38 and extending through a lumen 112 (as shown in FIG. 14) inthe handle 38. The actuator suture 110 can engage the locking clip 96through a first feed aperture 119 in the lower jaw 118 and can extendthrough a first actuator aperture 125 in the upper clip jaw 124 of thelocking clip 96. The actuator suture 110 can loop over the upper clipjaw 124 and can pass through a second actuator aperture 123 in the upperclip jaw 124. The actuator suture 110 can also extend through a secondfeed aperture 117 in the lower jaw 118 and back through the handle 38 toa second end attached to the clip actuator 108. Alternatively, theactuator suture 110 can be looped outside the handle 38, so that theoperator can pull the actuator suture 110 manually to draw the upperclip jaw 124 to engage the lower clip jaw 118 when the locking clip 96is in position to engage the left atrial appendage 12.

The first feed aperture 119 can be positioned through the lower clip jaw118 to allow the actuator suture 110 to pass through the lower clip jaw118 to the upper clip jaw 124. The upper clip jaw 124 can include thefirst and second actuator apertures 125, 123 that can allow the actuatorsuture 110 to loop around the upper clip jaw 124, while retaining aposition near the clip lock 126 on the upper clip jaw 124. The clipactuator 108 can be a movable actuator, similar to the torque screwassembly on the ring applicator shown in FIGS. 7 and 8, oralternatively, a thumb slide or lever. The clip actuator 108 can pullthe actuator suture 110 to engage the locking clip 96 by pulling theupper clip jaw 124 into engagement with the lower clip jaw 118 at theclip lock 126. The actuator suture 110 can include a first end coupledto the clip actuator 108. The first end can extend through the lumen 112passing through the lower jaw 118 to loop around the upper clip jaw 124and back through the lower clip jaw 118 to terminate at the handle 38.In this manner, the clip actuator 108 can bear against the actuatorsuture 110 to pull on the open end of the upper clip jaw 124 and toovercome the spring tenancy of the clip hinge 122 in order to draw theupper clip jaw 124 into a locking engagement with the lower clip jaw118.

The lower clip jaw 118 can include an engagement connection 121 toreleasably connect the locking clip 96 to the clip applicator 98 with aretention suture 111 (as shown in FIG. 14). The retention suture 111 canremovably attach the locking clip 96 to the clip applicator 98. Theretention suture 111 can include a first end coupled to the handle 38.The first end can extend from the handle 38 to the locking clip 96 toreleasably engage the lower clip jaw 118. As shown in FIG. 14, theretention suture 111 can loop into an engagement portion 121 of thelower clip jaw 118 so that the retention suture 111 may be cut at oneend. The retention suture 111 can be cut at the handle 38 to draw theretention suture 111 out of the patient and remove the clip applicator98, while leaving the locking clip 96 attached to the lower atrialappendage 12. As shown in FIG. 15, the engagement connection 121 caninclude an aperture in the lower clip jaw 118, adjacent the clip lock126, that can allow the retention suture 111 to pass into and around aportion of the lower clip jaw 118 and back to the handle 38.

As shown in FIGS. 14-17, a clip stop 114 and two alignment pins 116 canbe attached to a distal end of the handle 38. The lower clip jaw 118 caninclude one or more receivers (not shown) to receive the alignment pins116 in order to hold the locking clip 96 in alignment with the shaft 36and to prevent rotation of the locking clip 96 with respect to the shaft36. The clip stop 114 can include a retractable element in the shaft 36that can extend out to a position between the lower clip jaw 118 and theupper clip jaw 124. The clip stop 114 can extend out to engage thelocking clip 96 as the clip applicator 98 and the locking clip 96 arepassed through a lumen, tube, or endoscope, while the operator isinserting the locking clip 96 into a patient, in order to prevent thelocking clip 96 from inadvertently locking. After insertion through thelumen, the clip hinge 122 can bear against the clip jaws 118, 124 toopen the locking clip 96 for positioning around the base of the leftatrial appendage 12 or other target tissue, and the clip stop 114 can beretracted into the shaft 36.

FIG. 16 illustrates the clip 96 in an insertion position in which theclip stop 114 is removably engaged between the upper clip jaw 124 andthe lower clip jaw 118. The insertion position can help prevent the cliplock 126 from engaging as clip applicator 98 and the locking clip 96 arepassed into a patient's chest through an incision (possibly in a cannulaor endoscope). The clip actuator 108 can be used to pull the actuatorsuture 110 to move the clip stop 114 into the shaft 36 away from theclip jaws 118, 124. The clip actuator 108 can bring the clip jaws 118,124 into a position to lock the clip lock 126 and to hold the lockingclip 96 in a locking position, as shown in FIG. 16.

As shown in FIG. 17, the locking clip 96 can be disengaged from the clipapplicator 98 by cutting the retention suture 111 at the handle 38 anddrawing the retention suture 111 out of the clip applicator 98.Likewise, the actuator suture 110 can be released from the clip actuator108, can be cut, and can be pulled out of the patient and from the clipapplicator 98. The locked locking clip 96 can releasably slide off ofthe alignment pins 116 and can remain attached to the left atrialappendage 12 when the clip applicator 98 is removed.

FIGS. 18-20 illustrate one embodiment of an occluder including a clampwith a first pressure plate 152 and a second pressure plate 154. Thefirst and second pressure plates 152, 154 can each have one or more endholes 151. A ratcheting mechanism can include teeth 155 on connectorrods 153 and a receiver 157 for receiving the connecting rod 153 andengaging the teeth 155 to substantially permanently hold the plates 152,154 in spaced relation to one other in order to isolate the chamber ofthe left atrial appendage 12. As shown in FIG. 20, the receivers 157 canbe positioned onto the connector rods 153 extending from the secondpressure plate 154. The receivers 157 can bear against the firstpressure plate 152 to hold the plates 152, 154 in a predefined spacedrelation. As shown in FIG. 21, the ends of the connector rods 153extending from the receivers 157 can be clipped off after the desiredclaming is achieved.

FIGS. 21-22 illustrate one embodiment of an occluder in which thepressure plates 152, 154 can be configured with a tie channel 156passing through each plate 152, 154 from one end to another. A tie 158can be passed through the tie channels 156 to connect the first andsecond plates 152, 154 together. The plates 152, 154 can be positionedto clamp down on the base of the left atrial appendage 12 to close offthe left atrial appendage chamber 94.

FIGS. 23-29 illustrate one embodiment of a loop clip 174 and a loop clipapplicator 172 for engaging the left atrial appendage at its base inorder to close the chamber of the left atrial appendage. The loop clip174 can include a lower clip jaw 176 and a loop 178. The loop 178 caninclude a fixed end 187 attached to the lower clip jaw 176 and teeth 182that extend to a slidable end 185. The loop 178 can engage the lowerclip jaw 176 at a clip lock 183 to substantially permanently clamp bybearing against tissue trapped between the loop 178 and the lower clipjaw 176.

FIG. 26 illustrates an actuator attachment 180 that can include aretention suture 111 extending from the handle 38 to an engagementportion 177 on the loop clip 174. The engagement portion 177 can includean aperture through the loop clip 174 to allow the retention suture 111to extend from the handle 38, through the shaft 36 around the engagementportion, and back to the handle 38. The retention suture 111 canreleasably retain the loop clip 174 on the loop clip applicator 172,until the loop clip 174 is secured around the left atrial appendage. Theretention suture 111 can be cut at one end and drawn out of the patientto leave the loop clip 174 engaged.

FIG. 24 illustrates an actuator suture 110 attached to the slidable end185 of the loop clip 174. The actuator suture 110 can be removablyattached to the slidable end 185 of the loop 178 by looping through anactuator aperture 180. The fixed end 187 of the loop 178 can be attachedto the lower clip jaw 176 while the remainder of the loop 178 havingteeth 182 can slidably engage the clip lock 183.

As shown in FIG. 27, the loop clip 174 can be attached to the loop clipapplicator 172 and maintained in an insertable position. The loop clip174 and the shaft 36 can be inserted into the patient's chest to bringthe loop 178 to a position adjacent the left atrial appendage 12. Theloop clip 174 can be manipulated to a position where the lower jaw clip176 is adjacent the base of the left atrial appendage 12 and the loop178 extends around the left atrial appendage 12. The actuator suture 110can be attached to an actuator 108, which can include a knob 50 and atorque screw 82, as shown in FIG. 23. The knob 50 can be turned totraverse the hex head of the torque screw 82 to bear against theactuator suture 110 in order to pull the slidable end 185 of the loop178 through the clip lock 183 where the teeth 182 can be engaged by thelower jaw clip 176 to substantially permanently hold the loop 178 inposition. The knob 50 can be turned until the loop 178 is pulled astight as desired against the tissue of the left atrial appendage 12 inorder to isolate the chamber from the atrium. Alternatively, theactuator suture 110 can be looped outside the handle 38 to be pulledmanually by the operator to lock the loop clip 174 in relation the lowerclip jaw 176. Other embodiments of the actuator 108 can include a lineartrigger grip, a linear slider, etc.

As shown in FIG. 28, the loop clip 174, which is shown in a position forencircling and occluding the left atrial appendage to close the chamber94, can be disengaged from the loop clip applicator 172 by cutting oneend of the retention suture 111 and pulling the retention suture 111from around the engagement portion 177 and out of the patient's body. Asshown in FIG. 28, the loop 178 can be engaged by the teeth 182 to thelower clip jaw 176 to a closed position. The loop 178 can be disengagedfrom the loop clip applicator 172 by cutting one end of the actuatorsuture 110 and pulling the actuator suture 110 through the actuatoraperture 180 and out of the patient.

Some embodiments of the invention provide a tool designed to place aring-style left atrial appendage occlusion device. The tool can includea handle with a long neck. An upper and a lower jaw can be attached tothe handle with a four-bar assembly on a distal end and a knob 50 and atorque screw 82 on a proximal end. Some embodiments of the tool caninclude four separate sutures (2 front and 2 rear) that can loop arounda ring and then into the upper and lower jaws. The sutures can bepositioned in slots on outside edges of the upper and lower jaws anddown into the handle. A retaining suture can be positioned through thelower jaw of a ring into a distal end of the handle, and the loop can becompleted outside a proximal end of the tool. The retaining suture canbe used to pull and then hold the ring tight against the distal end ofthe handle. Two holes can be positioned in an end of the lower jaw ofthe ring. Alignment pins can be inserted into the two holes to help holdand position the ring. After routing through the handle, the retainingsuture can be positioned into the hex end of the torque screw andthrough to the other side where the retaining suture are then tied off.

According to some embodiments of a method of the invention, a port canbe placed in the patient's chest so that when the ring is placed andopened, the left atrial appendage can be pulled into the opening with agrasper, a vacuum source (e.g. a cone), an adhesive tool tip, a cryodevice for temporarily sticking to tissue, etc. A neck of the tool caninclude articulation to aid in placement of the ring. A distal end ofthe tool can be guided through the port and placed near the left atrialappendage. As the torque screw is turned, the upper and lower jaws openparallel to one another. Continuing to turn the torque screw stretchesthe ring open. Other methods of actuation can be used to pull thesutures, such as a trigger, slider, etc. When the ring is fully opened,the left atrial appendage can be pulled between the upper and lower jawsuntil properly located. The torque screw can be turned in the oppositedirection to release tension on the sutures and relax the ring aroundthe left atrial appendage. The torque screw can be tightened and relaxedmultiple times, if necessary to achieve proper placement. Once the ringis properly positioned, the sutures can be cut (either near the ring oron a proximal end of the tool) to release the ring, and the tool can beretracted. An inside edge of the port can be used to close the upper andlower jaws so the tool can be removed.

Other embodiments of the invention provide a tool designed to place aclip-style left atrial appendage occlusion device. The clip can be arigid one-piece clip with a snap-in lock on one end. The clip can alsoinclude a living hinge that is spring biased open on the other end.However, other embodiments of the tool can be used with other types ofrigid clips, as well as a different hinge or latching mechanism. Thetool can include a handle with a long neck. Two separate suture loopscan be positioned along the length of the handle inside the neck. A stopon a distal end of the tool can be actuated on a proximal end of thetool. An actuation suture can be positioned through an upper clip jaw ofthe left atrial appendage clip, then through a lower clip jaw, into adistal end of the handle and complete a loop outside a proximal end ofthe handle. A port can be created in the patient's chest such that whenthe clip is positioned near the left atrial appendage, the left atrialappendage can be pulled between the upper and lower clip jaws with agrasper. The neck on the tool can articulate to aid in placement of theclip. The stop can be placed in its forward position to keep the upperclip jaw from latching while pushing it through the port. The clip canspring open after it has passed through the port. The handle can be usedto position the clip near the left atrial appendage and the left atrialappendage can be pulled between the upper and lower clip jaws with agrasper. Once the clip is positioned on the left atrial appendage asdesired, a stop actuation knob 50 can be pulled back to retract thestop. The actuation suture can be pulled (or actuated with a trigger,slide, screw, etc.) until the upper clip jaw snap latches into the lowerclip jaw. The left atrial appendage is then occluded. The sutures can becut and pulled through the handle, which can release the clip. Thesutures can be cut with a scalpel, scissors, or other surgicalinstruments, or the sutures can be cut with a mechanism that is builtinto the tool itself. The tool can then be removed from the port.

Some embodiments of the invention provide a tool designed to place aloop-clip style left atrial appendage occlusion device. The tool caninclude a handle with a long neck. The tool can include two separatesuture loops that can be positioned through the length of the handle anda shaft. The tool can include a knob 50 and a torque screw on a proximalend of the handle and the shaft. The loop clip 174 can include a rigidbase with a flexible loop that can include one-way teeth molded into it.The loop can wrap around one end of the rigid member and through a slotwith a locking snap (like a cable tie). This allows the loop to bepulled in, but not release. The end of the loop can include a hole thata suture can be routed through. The suture can be positioned into thedistal end of the placement device, can be positioned through thehandle, into the hex end of the torque screw, and tied off on anopposite end. A retaining suture can be positioned through a hole in anend of the loop clip, then into a distal end of the placement device,positioned through the handle, and tied off on a proximal end of thetool. The retaining suture can be used to pull and hold the loop cliptight against a distal end of the handle. An alignment boss on an end ofthe handle can be inserted into a matching slot on the loop clip toensure proper alignment. A port can be created in the patient's chest sothat when the loop clip is positioned, the left atrial appendage can bepulled between the loop and the base with a grasper. The neck on theplacement tool can articulate to aid in placement of the loop clip. Theflexible loop can be pushed down to place the loop clip through theport, then once it is through, the loop can return to its originalshape. The handle can be used to position the loop clip near the leftatrial appendage and the left atrial appendage can be pulled inside theloop with a grasper. Once the loop clip is positioned on the left atrialappendage as desired, turning the torque screw can gradually tighten theloop (a trigger, slide, etc. could also be used to tighten the loop).The torque screw can be turned until the loop is tight enough to occludeflow and remain securely placed. After the loop is tight enough, theactuation suture and the retaining suture can be cut and pulled throughthe handle. The tool can then be removed from the port.

Some embodiments of the invention include a device and method forocclusion or ligation of an atrial appendage or other tissue. The methodand applicators disclosed herein describe a minimally-invasive approachto ligation of an atrial appendage, specifically, of the left atrialappendage of patients with atrial fibrillation. Some embodiments of theinvention include a method and apparatus to access the left appendagethrough a small incision and the use of a delivery tool to apply anoccluder to the appendage. The tool can be used to grasp the appendageto help stabilize the appendage to allow for application of the ligationdevice. The ligation device may be applied and left behind as apermanent implant.

Some embodiments of the invention include a device and procedure thatcan occlude the left atrial appendage from the body of the leftatrium—thereby substantially preventing the formation of a clot withinthe appendage and a subsequent embolism. Some embodiments of theinvention include an implantable device and applicator for substantiallypermanently occluding the left atrial appendage. Some embodiments of theinvention include a device and procedure that is minimally invasive toapply a device as a simple and quick method to deliver therapy toprevent embolic strokes. Some embodiments of the invention include adevice and procedure that does not require the use of blood-contactingbiomaterials. Some embodiments of the invention include a device andprocedure that results in tissue necrosis at the left atrium/left atrialappendage junction that is necessary to help prevent reentry. Someembodiments of the invention include a device and procedure that placesa device to occlude while preserving the tissue of the left atrialappendage for the production of atrial hormones. Some embodiments of theinvention include a device and procedure with a substantiallypermanently-implanted clamp used for occluding the left atrialappendage. Some embodiments of the invention include a device andprocedure that is applied from the exterior of the heart, which may beaccessed by a sternotomy, thorocotomy, minimally invasive, endoscopic orother means. Some embodiments of the invention include a device andprocedure that may be practiced by a number of different embodiments ofthe clamping mechanism as disclosed herein.

FIG. 30 illustrates a device 200 for ligation of an atrial appendage.The device 200 can include a ring applicator or delivery tool 202 and anocclusion member or ring 214. In one embodiment, the occlusion ring 214can be made of a 30A durometer silicone rubber, although otherhardnesses of silicone or other materials, such as polyurethane can beused. The ring 214 can be covered with a material such as Dacron®polyester to promote tissue ingrowth or prevent ring slippage afterplacement or to spread the load bearing surfaces of the ring. The ring214 can be generally expandable for placement around the atrialappendage. The delivery tool 202 can be used to expand the ring 214. Thedelivery tool 202 can include a shaft 220 and a handle 230 coupled toshaft 220. The delivery tool 202 can be sized for reaching an atrialappendage through an opening in the patient's chest, for example,through a sternotomy or thoracotomy. The delivery tool 202 can include atissue-grasping member 210. The tissue-grasping member 110 can be amechanical grasping member, for example, hooks, barbs, or graspers, orit can be a suction grasping member (as shown in FIG. 30), or it can bean adhesive. The delivery tool 202 can include one or more suctionlumens fluidly coupled to suction grasping member 210. The suctionlumens can pass through the shaft 220 and/or handle 230, or portionsthereof. The suction grasping member 210 can be coupled to a suctionsource. The tissue-grasping member 210 can be used to grasp the atrialappendage and pull it through ring 214. In one embodiment, thetissue-grasping member 210 can be moved distally and/or proximallyrelative to shaft 220. In one embodiment, the delivery tool 202 caninclude a mechanism for controllably moving the tissue-grasping member210. This mechanism can be located at or near the handle 230.

The delivery tool 202 can include a ring spreader 240 havingring-expanding members 242 used to hold and expand the ring 214. Thering spreader 240 can be coupled to a distal end of shaft 220. In oneembodiment, the delivery tool 202 can include multiple ring-expandingmembers 242, for example, four, as shown in FIG. 30. Alternatively, thedelivery tool 202 can include three or five expanding members 242, forexample. The ring 214 can be releasably coupled or attached to a distalend of ring-expanding members 242, for example, via one or more sutures250. The sutures 250 can loop around the ring 214. The ends of thesutures 250 can pass through one or more lumens within the ringexpanding members 242, the shaft 220, and the handle 230. In oneembodiment, one or more portions of the sutures 250 can be exposed at ornear distal or proximal ends of the handle 230. For example, portions ofsutures 250 can be exposed at a suture cutting location 270. Exposure ofthe sutures 250 at or near the handle 230 can enable the release of thering 214 from the delivery tool 202 remotely. In one embodiment, thesutures 250 can be cut and removed, thus releasing the ring 214 from thedelivery tool 202. Cutting the sutures 250 can release the ring 214 fromthe ring-expanding members 242. In one embodiment, the delivery tool 202can include one or more suture cutting members.

As shown in FIG. 30, the handle 230 can include a ring expansionmechanism 260 used to control the expansion of the ring 214. The ringexpansion mechanism 260 can be coupled to the ring-expanding members242. The ring expansion mechanism 260 can control movement of the ringexpanding members 242 from a closed or collapsed configuration to anopen or expanded configuration, as shown in FIG. 30. In one embodiment,the ring expansion mechanism 260 can include a screw mechanism. The ringexpansion mechanism 260 can control movement of the ring-expandingmembers 242 into and out of shaft 220. The pulling of the ring-expandingmembers 242 into the shaft 220 can collapse the ring-expanding members242 into a closed configuration. The pushing of the ring-expandingmembers 242 out of the shaft 220 can expand the ring-expanding members242 into an open configuration. The ring-expanding members 242 can bespring biased into an open expanded configuration.

In one embodiment, the ring expansion mechanism 260 can be located at ornear distal or proximal ends of the handle 230. In one embodiment, thering expansion mechanism 260 can include one or more knobs 261 and oneor more threaded members 262, as shown in FIG. 30.

As shown in FIG. 31, the delivery tool 202 can be placed around the leftatrial appendage 12 of a heart 20. FIG. 31 schematically illustrates thestructure of the left and right atria 11 and 21, respectively, as viewedfrom a posterior aspect, including the bases of the pulmonary veins 23and the bases of the superior vena cava and inferior vena cava 25 and27, respectively, which enter the right atrium 21. FIG. 31 alsoschematically illustrates the left and right atrial appendages 12 and22, respectively.

FIGS. 32 and 33 schematically illustrate an outline of the left atrium11 of the heart 20 with the left atrial appendage 12 protrudingtherefrom. The ring 214 can be placed in a position to surround the leftatrial appendage 12 adjacent to the left atrial appendage base 18 wherethe left atrial appendage 12 is attached to the heart 20. The ring 214can be made of an elastic material to allow it to be stretched into anopen or expanded position, as shown in FIG. 32. The ring 214 can beallowed to return to a closed or collapsed position, as shown in FIG.33, in order to bear against the tissue of the left atrial appendage 12and to substantially close off any interior connection between the leftatrium 11 and the left atrial appendage 12.

As shown in FIG. 32, the ring 214 can be attached to a patient's heart20 to isolate the left atrial appendage 12 from the left atrium 11. Insome embodiments, multiple rings 214 can be placed successively more andmore proximal to the base 18 of the left atrial appendage 12. Theelastic material of the ring 214 can be any biocompatible material,thereby allowing the ring 214 to be left on the heart 20 permanently. Inone embodiment, the ring 214 can have different relative sizes toaccommodate different anatomy requirements of the patient. The ring 214can be manufactured with radio opaque qualities, such as micro-sizedglass beads molded into the elastic material. Alternatively, the ring214 can be made radio opaque by the addition of glass or metallic fibersin the elastic material. The ring 214 can be entirely biocompatible toallow for use for the life of the patient. The ring 214 can have sizevariations in its inner diameter along a contact surface.

In one embodiment, surgical access to the left atrial appendage can bethrough a left-sided thoracotomy or laproscopic port incision. Thedelivery tool and attached collapsed ring can be inserted through theleft thoracotomy access. The ring can then be expanded. The left atrialappendage can be grasped and drawn or pulled through the expanded ring.The ring can be positioned toward the base of the left atrial appendageand released from the delivery tool. The delivery tool can then beremoved from the patient, and the incision can be closed. Variousimaging methods can be employed before, during, and after the tissueocclusion procedure. For example, contrast fluoroscopy, trans-thoracicultrasound, and/or trans-esophageal echo (TEE) can be employed. Othersurgical approaches are possible including sub-xyphoid.

As shown in FIG. 34, some embodiments of the invention provide anadjustable band occluder 314. The adjustable band occluder 314 caninclude a band 316, a loop 318, and an adjustment mechanism 320. Thesize of the loop 318 can be varied by moving the adjustment mechanism320 along the length of the band 316. The adjustable band occluder canbe locked in a fixed position by any suitable means, such as, but notlimited to, a crimper region, a ratchet mechanism or other mechanicalengagement structure, or other suitable locking mechanism.

Some embodiments of the invention address a number of problems, such assurgical access to the endocardial surfaces of the atrial chambers of abeating heart and permanent closure of the atrial appendage volume.These problems have been addressed by others using various methods anddevices, such as percutaneous catheters. The right atrium may beaccessed via transvenous catheters placed through a femoral vein in thegroin, as well as through superior veins such as the subclavian,brachiocephalic, or jugular veins. The left atrium is more difficult toreach transvenously, requiring first, right atrial access followed by atransseptal puncture through the fosa ovalis of the inter-atrial septuminto the left atrium. With these transvenous methods, only relativelysmall diameter catheters can be passed through the vasculature. Inaddition, these devices must be navigated using fluoroscopic guidance orsome form of electronic navigation.

Positioning and placement of the therapeutic elements of such catheterscan be a challenge, because the movement is controlled remotely from thepoint of venous access. From point of entry into the body to thetherapeutic end of the catheter, the distance may be 70-110 cm through adifficult path. In cases where tissue contact force is critical, thiscan be a significant problem. Stability of the catheter tip is an issuein a beating heart compared to firm control possible with much shorterand more rigid surgical implements. A number of commercially-availablecatheters may be able to be positioned in most areas of the atria, butonly one catheter-based device has been developed to permanently closeoff the left atrial appendage following a procedure. This device, knownas PLAATO (percutaneous left atrial appendage total occlusion) must becarefully sized to allow positioning within the left atrial appendagesuch that it is retained in position distal to the ostium with the leftatrial chamber. This presents a significant risk that the device may bereleased into the atrium and pass into the left ventricle and becomeentangled in the chordae tendinae supporting the mitral valve or becomelodged in the left ventricular outflow tract or aorta. The risks of sucha procedure were documented in an abstract by Fischer at the 2005meeting of the American College of Cardiology—Evelyn Fischer, et al.,“Left Atrial Appendage Occlusion to Prevent Stroke in SuboptimalWarfarin Candidates: Current Results of the European MulticenterRegistry Trial,” American College of Cardiology, Abstract presented at2005 National Meeting, which is herein incorporated by reference in itsentirety.

The atria may be accessed through sternotomy, thoracotomy, intercostalsports, or under the sub-xiphoid process. Access to the atria isimportant for treatment of atrial fibrillation (AF),atrial-septal-defects (ASD's), patent foramen ovalis (PFO), and mitralor tricuspid valve disease. Also of importance is the elimination of theleft atrial appendage volume at the end of the procedure in order toreduce stroke risk. Surgical removal and closure of the left atrialappendate has been accomplished by using a surgical stapler/ligationdevice or by suturing the appendage closed followed by surgical excisionof the distal appendage. This is not without risks as noted by Krum etal.—David Krum, David L. Olson, Daniel Bloomgarden, Jasbir Sra,“Visualization of Remnants of the Left Atrial Appendage followingEpicardial Surgical Removal,” Heart Rhythm (2004) 1,249. Such surgicalremoval may result in an incomplete reduction of the left atrialappendage and allow a volume to remain unclosed, which is hereinincorporated by reference in its entirety.

Regarding the relationship between the left atrial appendage and strokerisk, Blackshear et al. stated that left atrial appendage obliteration“is a routine part of modern ‘curative’ operations for nonrheumaticatrial fibrillation, such as the maze and corridor procedures.” JosephL. Blackshear, MD, John A. Odell, FRCS(Ed), “Appendage Obliteration toReduce Stroke in Cardiac Surgical Patients with Atrial Fibrillation,”Ann. Thorac. Surg., 1996; 61:755-759, which is herein incorporated byreference in its entirety. To assess the potential of left atrialappendage obliteration to prevent stroke in nonrheumatic atrialfibrillation patients, they reviewed previous reports that identifiedthe etiology of atrial fibrillation and evaluated the presence andlocation of left atrial thrombus by transesophageal echocardiography,autopsy, or operation.

They reviewed the results of twenty-three separate studies and foundthat 446 of 3,504 (13%) rheumatic atrial fibrillation patients, and 222of 1,288 (17%) nonrheumatic atrial fibrillation patients had adocumented left atrial thrombus. Anticoagulation status was variable andnot controlled for. Thrombi were localized to, or were present in theleft atrial appendage and extended into the left atrial cavity in 254 of446 (57%) of patients with rheumatic atrial fibrillation. In contrast,201 of 222 (91%) of nonrheumatic atrial fibrillation-related left atrialthrombi were isolated to, or originated in the left atrial appendage(p<0.0001). Their data suggested that left atrial appendage obliterationis a strategy of potential value for stroke prophylaxis in nonrheumaticatrial fibrillation. A device was developed that allows percutaneousleft atrial appendage transcatheter occlusion (PLAATO) via transseptalcatheterization. Initial studies in dogs demonstrated the ability of thedevice to seal the left atrial appendage. Sievert et al. reported theirinitial experience with PLAATO in a human clinical trial involving 15patients. Horst Sievert, MD et al, “Percutaneous Left Atrial AppendageTranscatheter Occlusion to Prevent Stroke in High-Risk Patients withAtrial Fibrillation,” Circulation, 2002, 105:1887, which is hereinincorporated by reference in its entirety.

PLAATO was purported to be a less invasive, percutaneous approach toclosing the left atrial appendage. Previous animal studies of the devicewith follow-up of up to 1 year have demonstrated occlusion of the leftatrial appendage with complete healing, absence of erosions, newthrombus formation on the device, or interference with atrial function.

In the initial cohort of 15 patients, occlusion of the left atrialappendage was successful in all, as proven by left atrial angiography.There were no complications associated with the device, either acutelyduring the implantation procedure or during follow-up. The onlycomplication during the study was hemopericardium in the first patientattempted, which was not device-related. It resulted from left atrialappendage access, and should be easily avoided with increasedexperience. The procedure was successful in a second attempt in thatpatient.

All patients did well in follow-up. One theoretical concern is thedevelopment of new thrombi on the implant. However, the use of ePTFE onthe implant surface should result in relatively benign healing.Histological examination in dogs undergoing PLAATO reveal partialendothelialization at 1 month, which is complete by 2 to 3 months. Inthese 15 patients, transesophageal echo (TEE) at 1 month showed thesurface to be completely smooth and free of mobile thrombi. FIG. 35illustrates a deployed PLAATO device. Fluoroscopic images ofnon-occluded left atrial appendage, deployment of the PLAATO device, andleft atrial appendage post-deployment can be taken.

A larger cohort of patients was included in the European PLAATO RegistryTrial by Fischer, et al. a study that was finished in January 2003 thatexamined the safety and feasibility of this procedure. This studydescribed the experience of 92 patients. Inclusion criteria were atrialfibrillation (AF) with inability to take Warfarin®, prior cerebralischemia and/or two clinical risk factors for stroke. After implantationof the PLAATO occluder, the patients were followed with X-ray, TEE andNIH stroke scale in regular intervals. Of the 92 patients, 67% were malewith a mean age of 70±9 years. All candidates were successfullyimplanted. The mean procedure time was 76±36 minutes and the mean leftatrial appendage orifice diameter was 20±3 mm. During follow up, onepatient died of a bronchial carcinoma diagnosed 3 months before the oneyear follow up. One patient sustained a stroke six months post implant.Thus, the yearly incidence of stroke after implantation is 1.9%. Withthis small number of patients, the estimated risk reduction was 55%.

Of concern, in three patients, a thrombus on the occluder was foundprior to hospital discharge (2) and one month after the procedure (1).All thrombi were resolved without sequelae. One device was chosen toosmall and embolized into the aorta after its release. It was snared witha catheter and was retrieved successfully. Another device was implantedsuccessfully in the very same procedure.

To summarize this group's experience with the PLAATO device, theincidence of stroke in high-risk patients may decrease afterimplantation of the device. Considerable risks exist with thisprocedure, including errant transseptal puncture resulting in aorticdissection or atrial free wall perforation resulting in tamponade,embolization of the PLAATO device resulting in device entanglement incardiac structures, along with thrombus formation on the occludersurface that could lead to emboli production and stroke. In addition,the chronic nature of this implant must be considered. Constant flextureof the nitinol wire structure may lead to long term fatigue andpotential fracture and perforation of cardiac or adjoining tissues.

The group of Odell et al, hypothesized that if the atrial appendagecould be safely obliterated, then the incidence of embolic stroke may belessened. John A. Odell, et al., “Thoracoscopic Obliteration of the LeftAtrial Appendage: Potential for Stroke Reduction,” Ann. Thorac. Surg.,1996, 61:565-569, which is herein incorporated by reference in itsentirety. If the appendage can be obliterated using a thoracoscopictechnique, a procedure of lesser magnitude than thoracotomy, then it mayoffer an alternative form of management for patients ineligible forWarfarin® therapy. To determine the feasibility of atrial appendageobliteration done using the thoracoscope, they performed the procedurein mongrel dogs and in human cadavers.

Transesophageal echocardiography with emphasis on visualization of theleft atrial appendage was performed pre-, intra-, and postoperatively.In five dogs, the atrial appendage was obliterated with staples, and infive the appendage was obliterated with an endoloop of 0 Vicryl suturematerial. Three ports were made—one in approximately the seventhinterspace approximately 5 cm from the midsternum (port 1), a secondinserted anteriorly in the fourth interspace (port 2), and a third moreposteriorly in the fourth interspace (port 3). Carbon dioxide wasinstilled to a pressure of 4 to 10 mm to collapse the lung. In allanimals, the pericardium was opened anterior and parallel to the phrenicnerve. Gordon N. Olinger, MD, “Carbon dioxide displacement of left heartchambers,” J. Thorac. Cardiovasc. Surg., 1995, 109:187-188, which isherein incorporated by reference in its entirety.

Through the first port, the camera was inserted; through the secondport, the pericardium was grasped with an instrument; and, usingscissors inserted through the third port, the pericardium was opened.The technique then varied depending upon whether the appendage wasobliterated with staples or with the endoloop. In those having theappendage stapled, the camera was withdrawn from port 1 and inserted inport 3. Through port 1, a 35 endo GIA stapler (Ethicon Endosurgery,Cincinnati, Ohio) with the knife blade removed was inserted, positionedacross the base of the atrial appendage, and fired. In dogs having theappendage obliterated with the endoloop (Ethicon), the camera positionwas not changed. The endoloop was introduced through port 3 and theappendage was grasped through the loop of the suture. The loop waspositioned across the base of the appendage and then tightened.

At 11 weeks, the dogs were again anesthetized with sodium pentobarbital(30 mg/kg intravenously) and a midline sternotomy was made. The heartwas examined using epicardial echocardiography. The dogs wereeuthanized, the hearts were removed, and the left atrium was inspected.

The procedure also was attempted in eight human cadavers. In thecadavers, three ports were used for access. The most appropriate sitesappeared to be the second interspace anteriorly in the midclavicularline (for grasping the pericardium and the atrial appendage), the sixthinterspace in the midclavicular line (for the camera or staplinginstrument), and the fifth interspace in the anterior axillary line(usually for the scissors to open the pericardium, but also for thecamera or for the stapling instrument). The procedure as performed inthe dog and human experiments is illustrated in FIGS. 36A-E.

The group of DiSesa investigated the use of an automatic surgicalstapler for ligation of the atrial appendage in sheep, and then appliedthis technique in patients. V. J. DiSesa, S. Tam and L. H. Cohn,“Ligation of the Left Atrial Appendage using an Automatic SurgicalStapler,” The Annals of Thoracic Surgery, Vol. 46, 652-653, which isherein incorporated by reference in its entirety. Fourteen adult sheepunderwent ligation of the left atrial appendage using a surgical staplerwith a rotating head and either absorbable or stainless steel staples.In four sheep, killed after two hours, no hemorrhage or intra-atrialthrombus was observed acutely. Ten sheep were allowed to recover for 90to 100 days, twice the expected absorption time of absorbable staples.There was complete obliteration of the left atrial appendage withoutevidence of intra-atrial thrombus or staple migration. The absorbablestaples were completely reabsorbed. They subsequently used thistechnique in five patients undergoing mitral valve procedures. Therewere no complications, and adequate obliteration of the atrial appendagewas achieved. Other reports indicate that staples may require the use ofreinforcement strips to prevent bleeding and tissue tearing.

Considering the simple surgical ligation methods, the group of Katz, etal. studied the incidence of incomplete ligation of the left atrialappendage during mitral valve surgery. Edward S. Katz MD, FACC,Theofanis Tsiamtsiouris MD, Robert M. Applebaum MD, FACC, ArthurSchwartzbard MD, FACC, Paul A. Tunick MD, FACC and Itzhak Kronzon MD,FACC, “Surgical Left Atrial Appendage Ligation is Frequently Incomplete:A Transesophageal Echocardiographic Study,” Journal of the AmericanCollege of Cardiology, Volume 36, Issue 2, 1 August 2000, Pages 468-471,which is herein incorporated by reference in its entirety. Usingtransesophageal Doppler echocardiography, they studied 50 patients whounderwent mitral valve surgery and ligation of the left atrialappendage. Incomplete left atrial appendage ligation was detected in 18of 50 (36%) patients. This study demonstrated that surgical left atrialappendage ligation is frequently incomplete. Residual communicationbetween the incompletely ligated appendage and the left atrial body mayproduce a milieu of stagnant blood flow within the appendage and be apotential mechanism for embolic events. Ligation of the left atrialappendage is frequently performed during mitral valve surgery toeliminate a potential source of emboli. However, the success ofcompletely excluding the left atrial appendage from the circulation hadnot previously been systematically addressed. Transesophagealechocardiography offers unique visualization of the appendage in thebeating heart and can evaluate the integrity of the surgical ligation.Usually, when the left atrial appendage is ligated, its cavity isobliterated with clot (since no flow enters the cavity) and cannot beseen during echocardiography. This appearance was the same whether thepatient was studied in the operating room or months after the surgery.When the appendage is incompletely ligated, not only can the appendagecavity be visualized but flow can be seen within the appendage, as wellas through an opening in the ligation site.

The group discovered that 36% of the time the left atrial appendage wasfound to be incompletely ligated after attempts at excluding it from theleft atrial body. Factors, such as an enlarged left atrium orsignificant mitral regurgitation, which may be thought to increase leftatrial tension and pressure (perhaps predisposing to incomplete ligationor dehiscence of sutures), did not appear to correlate with thisfinding. They also did not observe a correlation between appendage sizeand the incidence of incomplete ligation. In addition, the surgicalprocedure (mitral repair or replacement) and operative approach(traditional sternotomy or minimally invasive approach) did not changethe incidence of incomplete ligation. It is possible, however, that thesample size in this report may have been too small to exclude asignificant effect of these variables on the development of incompleteleft atrial ligation.

Incomplete left atrial appendage ligation was as commonly seen in theoperating room, evaluating the patient by transesophagealechocardiography immediately after terminating cardiopulmonary bypass,as it was seen in the laboratory evaluating patients referred fortransesophageal echocardiography at various times after the surgery.This suggested that incomplete left atrial appendage ligation is not adegenerative process with suture dehiscence over time, but rather ispresent immediately after the initial surgery. Incomplete ligation maybe secondary to several surgical factors. First, the running suturesused may not start and end exactly at the most distal edges of theatrial appendage, which may not be recognized with the appendage emptyand unstretched while on cardiopulmonary bypass during surgery. Inaddition, caution must be taken during appendage ligation to avoid deepsuture bites, which may involve the left circumflex coronary artery orits branches that may course in the area. This meticulous care may leadto shallower suture bites that may dehisce when the LA is once againfilled and stretched after cardiopulmonary bypass. Both of thesemechanisms may play a role, as in many cases flow was detected both atthe edge of the appendage orifice (apparently around the end of thesuturing line) and through an area at the midpoint of the appendageorifice (through the suture line). One group reported six cases ofincomplete left atrial appendage ligation when a purse string suture wasused to accomplish the ligation, a technique different from that used bysurgeons. The actual incidence, however, of incomplete left atrialappendage ligation using their technique was not addressed.

The clinical significance of an incompletely ligated left atrialappendage has never been studied. Theoretically, creating a smallcommunication between the LA and left atrial appendage may producestagnation of low velocity blood flow within the atrial appendage. Theappendage would then be a model for thrombus formation and continue toserve as a potential source of embolization since a port of entry intothe systemic circulation still exists. Although the numbers in thisstudy were small, several observations support this theory. First,spontaneous echo contrast (a marker for stagnant blood flow and aprecursor of thrombus formation) was seen within the appendage in halfof the patients with incomplete ligation. Second, and perhaps moreimportantly, in two-thirds of patients with spontaneous echo contrastwithin the incompletely ligated appendage, the contrast was actuallydenser within the appendage than within the left atrial body, suggestinga more stagnant and thrombogenic milieu. In two patients, frank thrombuswas seen within the incompletely ligated appendage.

The ultimate question, however, is whether patients with incompletelyligated left atrial appendages will have a higher incidence ofthromboembolic events. In the Katz study, four patients withincompletely ligated appendages had such events (one patient withStarr-Edwards prosthesis, two with St. Jude prosthesis and one patientstatus after mitral repair). This is quite a high number consideringthat only eight patients with incomplete ligation had any potential forlong term follow-up (the other ten patients with incomplete ligationwere discovered in the operating room). However, one cannot excludeother etiologies for embolization (as mechanical prostheses or atrialfibrillation) and referral bias still clouds this issue. Certainly,conventional ligation methods must be questioned in light of thefindings of this study.

A number of devices for occlusion of ASD's have been investigated.Melhem J. A. Sharafuddin, MD; Xiaoping Gu, MD; Jack L. Titus, MD, PhD;Myra Urness, BS; J. J. Cervera-Ceballos, MD; Kurt Amplatz, MD,“Preliminary Results With a New Self-Expanding Nitinol Prosthesis in aSwine Model Transvenous Closure of Secundum Atrial Septal Defects,”Circulation, 1997, 95:2162-2168, which is herein incorporated byreference in its entirety. Most of these concepts involve percutaneousdelivery from femoral vein access. Varying levels of success have beenachieved. Device dislodgment can occur if the size of the defect greatlyexceeds the waist diameter of the device or approaches the diameter ofthe retention buttons. On the other hand, placement of adisproportionately large device may result in mushrooming of theretention buttons and weakening of the cross-clamping forces against theseptal rim, which increases the risk of blood flow behind the discs andmay result in incomplete endothelialization. In addition, follow-upstudies of a clamshell occlusion device reported a delayed rate of metalfatigue fractures of one or more arms of about 30%. The Amplatzer deviceis shown in FIGS. 37A-E.

A small introduction system, simple and reliable placement technique,and favorable initial experimental success may provide promisingpotential of such a device for the percutaneous closure of secundum ASDsin all age groups. Heparinization is advocated in clinical use to lowerthe risk of catastrophic systemic embolization.

ASD device thrombosis is likely to be similar to thrombosis to beexpected on left atrial appendage closure devices. This makes the studyby Krumsdorf et al, on the incidence, morphology, and clinical course ofthrombus formation after catheter closure of ASD closure devices ofinterest regarding devices such as PLAATO. Krumsdorf U, Ostermayer S,Billinger K, Trepels T, Zadan E, Horvath K, Sievert H, “Incidence andClinical Course of Thrombus Formation on Atrial Septal Defect andPatient Foramen Ovale Closure Devices in 1,000 Consecutive Patients,” J.Am. Coll. Cardio., Jan. 21, 2004. 43(2):302-9, which is hereinincorporated by reference in its entirety.

A total of 1,000 consecutive patients were investigated after patentforamen ovale (PFO) (n=593) or atrial septal defect (ASD) (n=407)closure. Transesophageal echocardiography (TEE) was scheduled after fourweeks and six months. Additional TEEs were performed as clinicallyindicated. Thrombus formation in the left atrium (n=11), right atrium(n=6), or both (n=3) was found in 5 of the 407 (1.2%) ASD patients andin 15 of the 593 (2.5%) PFO patients (p=NS). The thrombus was diagnosedin 14 of 20 patients after four weeks and in 6 of 20 patients later on.The incidence was: 7.1% in the CardioSEAL device (NMT Medical, Boston,Mass.); 5.7% in the StarFLEX device (NMT Medical); 6.6% in the PFO-Stardevice (Applied Biometrics Inc., Burnsville, Minn.); 3.6% in the ASDOSdevice (Dr. Ing, Osypka Corp., Grenzach-Wyhlen, Germany); 0.8% in theHelex device (W.L. Gore and Associates, Flagstaff, Ariz.); and 0% in theAmplatzer device (AGA Medical Corp., Golden Valley, Minn.). Thedifference between the Amplatzer device on one hand and the CardioSEALdevice, the StarFLEX device, and the PFO-Star device on the other handwas significant (p<0.05). For a device such as PLAATO, specificallydesigned to reduce or eliminate thromboembolic events coming from theregion of the implant, occurrence of thrombus on ASD devices is aconcern.

A method and apparatus for thoracoscopic intracardiac procedures wasdescribed U.S. Pat. No. 6,401,720, entitled “Method and Apparatus forThoracoscopic Intracardiac Procedures,” Stevens, John H.; Palo Alto,Calif. 94303, Reitz, Bruce A.; Stanford, Calif. 94305, Roth, Alex T.;Redwood City, Calif. 94061, Peters, William S.; Woodside, Calif. 94062,Gifford, Hanson S.; Woodside, Calif. 94062, which is herein incorporatedby reference in its entirety. They described devices, systems, andmethods provided for accessing the interior of the heart and performingprocedures therein while the heart is beating. In one embodiment, atubular access device having an inner lumen is provided for positioningthrough a penetration in a muscular wall of the heart, the access devicehaving a means for sealing within the penetration to inhibit leakage ofblood through the penetration. The sealing means may comprise a balloonor flange on the access device, or a suture placed in the heart wall togather the heart tissue against the access device. An obturator isremovably positionable in the inner lumen of the access device, theobturator having a cutting means at its distal end for penetrating themuscular wall of the heart. The access device is preferably positionedthrough an intercostal space and through the muscular wall of the heart.Elongated instruments may be introduced through the tubular accessdevice into an interior chamber of the heart to perform procedures, suchas septal defect repair and electrophysiological mapping and ablation. Amethod of septal defect repair includes positioning a tubular accessdevice percutaneously through an intercostal space and through apenetration in a muscular wall of the heart, passing one or moreinstruments through an inner lumen of the tubular access device into aninterior chamber of the heart, and using the instruments to close theseptal defect. Devices and methods for closing the septal defect witheither sutures or with patch-type devices are disclosed. While thisconcept allows access to the heart chambers similar to the presentinvention, it does not provide for a simple means of incisional closureas do some embodiments of the invention.

Some embodiments of the invention may provide any one or more of thefollowing advantages: a single point of access for surgical treatment ofatrial fibrillation; fewer inter-costal access ports may be needed fortreating atrial fibrillation, as opposed to existing minimally-invasivemethods; blunt dissection of cardiac tissue is generally not required;pericardium is left substantially intact, except for a small incision;access to the heart for delivery of therapies for various diseasestates; a single device can provide surgical access to the heartchambers, as well as providing a means of closing the point of access atthe end of the procedure; and the left atrial appendage can be ligatedand/or eliminated at the close of the procedure with little or no riskof tearing. The left atrial appendage can be eliminated at the close ofthe procedure such that a residual remaining volume which could lead tostrokes is avoided.

Some embodiments of the invention provide a device that can provideaccess to the interior of the heart chambers. The device can allow forsingle point access to treat atrial fibrillation, atrial-septal defects,patent foramen ovalis, and valvular disease, as well as otherarrhythmias. Some embodiments of the device can be used to access theventricles from the access achieved through either appendage.Ventricular septal defects can be addressed. The device can be appliedto other body structures, such as the stomach where a portion of thestomach wall could be ligated by the elastic band and excluded. This maybe suitable as a treatment for obesity.

Some embodiments of the invention provide methods and devices to allowentry into the atria of a beating heart to perform delivery of therapyto the structures within the heart and endocardial surfaces and valvesassociated with the heart chambers. Upon removal of the device from theappendage, a permanent closure and elimination of the appendage volumecan be affected. More specifically, the entry points can be located inthe left and right atrial appendages. Of these, the left atrialappendage may be most appropriate, because closure and elimination ofthis appendage following a procedure has become a standard surgicalpractice performed by many surgeons.

According to embodiments of the method of the invention, pre-procedureincludes placement of one or two chest wall access ports forvisualization and placement of the invention. The lung can be deflatedand a small opening in the pericardium can be made adjacent to the leftatrial appendage. FIG. 38 schematically illustrates the relativelocations of structures of the heart and chest of interest regarding theinvention. More specifically, the left atrial appendage is shown in astretched state without the pericardium in place. The heart structuresnoted on FIG. 38 include the following: SVC—superior vena cava,IVC—inferior vena cava, TV—tricuspid valve, FO—fossa ovalis, MV—mitralvalve, PV—pulmonary vein, and left atrial appendage—left atrialappendage. FIGS. 39-68 illustrate devices and methods of using thedevices according to various embodiments of the invention. In someembodiments, a device 400 can include an elastic cinch ring 410, ringexpansion arms 412, and a portal tube assembly 414. The ring expansionor cinch ring support arms 412 can include three or four arms. Thedevice 400 can be positioned through a chest port 416 in a portion ofthe chest wall 418. The device 400 can be passed through a chest port416 placed between the ribs. The anatomical drawings of FIGS. 39-57 havebeen simplified to show only the left atrial appendage and the chestwall.

FIG. 39 illustrates the elastic cinch ring 410 in a contracted state.FIG. 40 illustrates the device 400 being advanced toward the left atrialappendage. FIG. 41 illustrates a suction cup or Babcock grasper probe420 being advanced through the portal tube assembly 414.

FIG. 42 illustrates the suction cup or Babcock grasper probe 420 beingattached to an end of the left atrial appendage. In other embodiments,any suitable type of grasper, vacuum device, adhesive, cyrogenic device,or nanotechnology device can be used to grasp and pull the left atrialappendage. FIG. 43 illustrates the support arms 412 being expanded andthe left atrial appendage being pulled toward the portal tube assembly414. FIG. 44 illustrates the cinch ring 410 being advanced over the leftatrial appendage. FIG. 45 illustrates the cinch ring 410 beingpositioned over the mid to proximal left atrial appendage.

FIG. 46 illustrates the cinch ring 410 being allowed to contract overleft atrial appendage and occlude a lumen 422 of the left atrialappendage. FIG. 47 illustrates the suction cup or Babcock grasper probe420 removed from portal tube assembly 414. FIG. 48 illustrates adilator/sheath assembly 424 including a dilator 426 and a sheath 428being advanced through the portal tube assembly 414. In someembodiments, prior to puncturing into the atrial appendage, the thoraciccavity can be inflated with carbon dioxide gas. Carbon dioxide inflationof the pericardial space can be used to lessen the prevalence andconsequences of air embolism, can help limit the chances of airintroduction, and can help limit bleeding. FIG. 49 illustrates a needleor sharp wire 430 being advanced through a lumen of the dilator 426 topuncture into the left atrial appendage lumen 422.

FIG. 50 illustrates the dilator 426 being advanced into the lumen 422 ofthe left atrial appendage and the needle 430 retracted. FIG. 50illustrates the sheath 428 being advanced over the dilator 426 into theleft atrial appendage lumen 422. FIG. 51 illustrates the left atrialappendage being filled with heparinized saline, as blood and air areremoved. As shown in FIG. 52, the left atrial appendage lumen 422 can beaspirated of blood 432 and flushed with heparinized saline using asyringe 434 to prevent thrombus formation. As shown in FIG. 53, the leftatrial appendage lumen 422 can be filled with heparinized saline asblood and air are removed. However, in some embodiments, it may bedesirable to allow blood to form a thrombus in the remaining left atrialappendage volume to promote healing and absorption of the closed-offportion of the left atrial appendage by surrounding tissue.

As shown in FIG. 54, the dilator 426 can be advanced past the cinch ring410 and into the left atrium. As shown in FIG. 55, the sheath 428 can beadvanced over the dilator 426 past the cinch ring 410 and into the leftatrium. As shown in FIG. 56, the dilator 426 can be removed. Ahemostasis valve (not shown) can be positioned on a proximal end of thesheath. As shown in FIG. 57, therapeutic implements can be advanced intothe left atrium for the treatment of various conditions.

FIG. 58 illustrates one embodiment of a balloon ablation device 436positioned at the right inferior pulmonary vein ostium. The use of acryogenic or high-intensity focused ultrasound balloon ablation devicecan be used in some embodiments of the invention. FIG. 59 illustratesone embodiment of a balloon ablation device 436 positioned at the leftsuperior pulmonary vein ostium.

FIG. 60 illustrates one embodiment of an encircling ablation device 438approaching the left superior pulmonary vein ostium. The ablation device438 can use radiofrequency (RF) energy, cryothermy, high-intensityfocused ultrasound, microwaves, or any other suitable ablation energy.FIG. 61 illustrates one embodiment of an encircling ablation device 438placed around the left superior pulmonary vein ostium.

FIG. 62 illustrates one embodiment of a left atrial de-bulking spiralablation device 440 placed against the posterior left atrium. FIG. 63illustrates one embodiment of a high intensity focused ultrasoundablation device 442 that can create a lesion over the left atrialisthmus. FIG. 64 illustrates one embodiment of a PFO or ASD closuredevice 444 being deployed in the fossa ovalis of the inter-atrialseptum. FIG. 65 illustrates one embodiment of a linear ablation device446 forming connecting lesions between the pulmonary veins.

As shown in FIG. 66, at the completion of all the endocardialtherapeutic procedures, the elastic cinch ring 410 can be allowed toconstrict down around the base of the left atrial appendage. The suturesor other devices holding the cinch ring 410 can be released such thatthe support arms 412 and the portal tube assembly 414 can be pulled awayfrom the heart, while leaving the cinch ring 410 substantiallypermanently in place at the base of the appendage. As shown in FIG. 67,immediately following the procedure, the left atrial appendage willgenerally include a volume that is contained by the cinch ring 410.Healing will then occur and the vestige of the left atrial appendagewill be absorbed into the atrial wall. As shown in FIG. 68, afterapproximately 12 weeks, the left atrial appendage is expected to havebeen absorbed and assimilated by the atrial wall. The ring 410 canremain embedded in the remaining scar 448.

FIGS. 69-71 illustrate a device 500 for ligation of an atrial appendage.The device 500 can include a ring applicator or delivery tool 502 and anocclusion member or ring 514. In one embodiment, the occlusion ring 514can be made of a 30A durometer silicone rubber, although otherhardnesses of silicone or other materials, such as polyurethane can beused. The ring 514 can be covered with a material such as Dacron®polyester to promote tissue ingrowth or prevent ring slippage afterplacement or to spread the load bearing surfaces of the ring. The ring514 can be generally expandable for placement around the atrialappendage. The delivery tool 502 can be used to expand the ring 514. Thedelivery tool 502 can include a shaft 520 and a handle 530 coupled toshaft 520. The delivery tool 502 can be sized for reaching an atrialappendage through an opening in the patient's chest, for example,through a sternotomy or thoracotomy. The delivery tool 502 can include atissue-grasping tool channel 570 extending from the handle 530 to thedistal end of the shaft 520. A tissue-grasping tool 580 may be movablypositioned within tissue-grasping tool channel 570. For example, shaft584 of tissue-grasping tool 580 fits within tool channel 570. In oneembodiment, tissue-grasping tool 580 may include one or more hooks,barbs, suction ports and/or graspers. For example, as shown in FIGS. 72and 73, tissue grasping tool 580 may include tissue graspers 582. Thetissue-grasping tool 580 can be used to grasp the atrial appendage andpull it through ring 514. In one embodiment, the tissue-grasping tool580 can be moved distally and/or proximally relative to shaft 520.

In one embodiment, the delivery tool 502 can include a ring spreader 540having a pair of ring-expanding members 542 used to hold and expand thering 514. The ring spreader 540 can be coupled to a distal end of shaft520. The ring 514 can be releasably coupled or attached to the distalends of ring-expanding members 542 and the distal end of shaft 520, forexample, via one or more sutures 550. The sutures 550 can loop aroundthe ring 514. The ends of the sutures 550 can pass through one or morelumens within the ring expanding members 542, the shaft 520, and thehandle 530. In one embodiment, the two ring-expanding members 542 openring 514 into a triangular shape. The proximal ends of thering-expanding members 542 are pivotally coupled to the distal end ofshaft 520, thereby allowing the ring-expanding members 542 to pivot froma closed or collapsed position, as shown in FIG. 69, to an open orextended position, as shown in FIG. 70. In the collapsed position,ring-expanding members 542 run parallel to shaft 520 and the distal endsof the ring-expanding members 542 point in a direction towards handle530. In the extended position, ring-members 542 are alignedperpendicular to each other and to shaft 520. In the extended position,ring 514 has an open triangular configuration, as shown in FIG. 70. Inone embodiment, sutures 550 are used to control the opening and closingof ring-expanding members 542. Sutures 550 run through suture lumens 525of shaft 520. The proximal ends of sutures 550 are attached or coupledto suture tension knob or ring expansion mechanism 532 located at handle530. Suture tension knob 532 is rotatable and may include a ratchetingmechanism. The ratcheting mechanism may be used to keep tension on thesutures without having to continuously hold onto knob 532. As knob 532is rotated, sutures 550 stretch ring 514 toward the distal ends ofring-expanding members 542 and actuate ring-expanding members 542 tomove from a collapsed configuration to an extended configuration whereinring 514 is opened into a triangular configuration. Ring 514 may bereleased when desired, for example, around tissue via actuation ofsuture cutting mechanism 562. Suture cutting mechanism 562 is used tocut sutures 550, thereby releasing ring 514 from delivery tool 502remotely. Suture cutting mechanism 562 includes cutting blade 564, whichis used to cut sutures 550.

In one embodiment, shaft 520 is approximately 12 mm in diameter and toolchannel 570 is approximately 5.5 mm in diameter. In one embodiment, toolchannel 570 provides guidance for positioning and manipulatingtissue-grasping tool 580. In addition, tool channel 570 allows delivertool 502 and tissue-grasping tool 580 to be positioned together througha single port, for example, a 12 mm port placed between the patient'sribs and it allows the two tools to be held by one hand.

In one embodiment of the present invention, the distal end of deliverytool 502 may be passed through a port or small incision, for example, inthe chest of a patient and positioned adjacent the left atrial appendageof a heart. Next, knob 532 may be rotated, thereby opening ring 514. Atissue-grasping tool 580 may then be slid distally along tissue-graspingtool channel 570 so that graspers 582 protrude through ring 514.Graspers 582 may then be manipulated by handle 586 to grasp tissue ofthe left atrial appendage. Tissue-grasping tool 580 and delivery tool502 are then manipulated so as to position a desired portion of the leftatrial appendage within the triangular opening of ring 514. Ring 514 isthen released from delivery tool 502 and allowed to constrict tissue ofthe left atrium.

The ring or band occluders and the clip occluders disclosed herein canbe constructed of any one or more of the following materials: siliconerubber, polyurethane, super-elastic material, shape-memory polymer ormetal, latex, nitrile, butyl, styrene-butadiene, polyacrylate, acrylic,polyisoprene, chloroprene, fluoroelastomers, or other suitablebiocompatible elastomeric materials. The ring or band occluders and theclip occluders disclosed herein can incorporate any one or more of thefollowing features: texturing to aid in mechanical stability (i.e.,ridges, bumps, grooves, etc.); fabric such as Polyethyleneterapthalate(i.e., Dacron®), polyester, ePTFE, etc. to promote tissue ingrowth;other types of coatings to promote tissue ingrowth; and pharmacologicalagents (e.g. a controlled release agent) to aid in tissue ingrowth,local therapeutic apoptosis, local necrosis, revascularization,arrhythmia control, infection control, anti-bacterial, fluid balance(i.e., atrial natritic peptide replacement).

In some embodiments of the invention, the ring or band occluders and/orclip occluders may incorporate one or more pharmacological agentsincluding anti-inflammatory agents (e.g., steroids, dexamethasone,beclomethasone) anti-arrhythmic agents, chemotherapeutic agents,anti-infection agents, anticoagulant agents, anti-thrombotic agents(e.g., coumadin, heparin), clotting agents, platelet agents, cytotoxicagents, growth factors, angiogenesis factors, hormones (e.g., atrialnatriuretic peptide), nitric oxide, radioactive agents, radiopaqueagents (e.g., barium sulfate), echogenic agents (e.g., perfluorocarbon),antibodies, antigens, immunoglobulins, enzymes, neurotransmitters,cytokines, blood agents, regulatory agents, transport agents, fibrousagents, proteins, peptides, proteoglycans, toxins, antibiotic agents,antibacterial agents, antimicrobial agents, bacterial agents, hyaluronicacid, polysaccharides, carbohydrates, fatty acids, catalysts, vitamins,DNA segments, RNA segments, nucleic acids, lectin, antiviral agents,viral agents, genetic agents, ligands, drugs and dyes (e.g., which actas biological ligands). One or more drugs or gents may be found innature (naturally occurring) and/or may be chemically synthesized.

One or more drugs or agents may be incorporated into the ring, band orclip, e.g., within a polymeric material of the ring, band or clip. Oneor more drugs or agents may be incorporated into one or more coatings ofthe ring, band or clip, e.g., within a polymeric coating covering atleast a portion of the ring, band or clip. One or more drugs or agentsmay be incorporated into one or more fabrics of the ring, band or clip,e.g., within or on a fabric coating covering at least a portion of thering, band or clip. In some embodiments of the invention, one or moredrugs or agents may be loaded uniformly throughout one or more materialsof the ring, band or clip. In some embodiments of the invention, one ormore drugs or agents may be loaded non-uniformly in one or morematerials of the ring, band or clip. In some embodiments of theinvention, one or more drugs or agents may be loaded within an innercircumference of the ring, band or clip. In some embodiments of theinvention, one or more drugs or agents may be loaded within an outercircumference of the ring, band or clip.

In some embodiments of the invention, one or more materials incorporatedinto the ring, band or clip may be “smart materials” which may altertheir structure in response to one or more external factors, e.g.,temperature. For example, the application of heat may cause a material,e.g., a polymer, to change shape or conformation, thereby resulting inthe release of a drug or agent. In one embodiment, ultrasound, e.g.,focused ultrasound, may be used to create heat needed to cause thematerial change shape or conformation.

In some embodiments of the invention, the ring, band or clip maycomprise one or more radiopaque materials, e.g., barium sulfate, therebymaking the ring, band or clip observable during fluoroscopic procedures.In some embodiments of the invention, the ring, band or clip maycomprise one or more echogenic materials, e.g., perfluorocarbon, therebymaking the ring, band or clip observable during ultrasound procedures.

In some embodiments of the invention, the ring, band or clip may releaseone or more drugs or agents via a diffusion-controlled mechanism. Forexample, a drug or agent may be uniformly or non-uniformly dispersed ordissolved in a material, e.g., a polymeric material, of the ring, bandor clip and/or a coating of the ring, band or clip and/or a fabriccovering of the ring, band or clip. The drug or agent may diffuse froman area of high concentration (e.g., from the material(s) of the band orclip) to an area of low concentration (e.g., an area of tissue such asthe LAA).

In some embodiments of the invention, the ring, band or clip may releaseone or more drugs or agents via a biodegradable mechanism. For example,a drug or agent may be uniformly or non-uniformly dispersed or dissolvedin a material, e.g., a polymeric material, of the ring, band or clipand/or a coating of the ring, band or clip and/or a fabric covering ofthe ring, band or clip. The drug or agent may be released duringdegradation of the material. The material may be designed to eitherdegrade completely or to degrade partially, e.g., leaving the corestructure of the material intact.

In some embodiments of the invention, the ring, band or clip maycomprise a cross-sectional shape that may be round, square, rectangular,oval, triangular, star-shaped, etc. In some embodiments of theinvention, the ring, band or clip may be reversibly placed, and itsposition may be adjusted if necessary. In some embodiments of theinvention, multiple ring, band or clip may be placed more and moreproximal to the base of the left atrial appendage.

In some embodiments of the invention, the ring, band or clip may includeone or more sensors, for example to monitor changes in one or moretissue properties. One or more properties of surrounding tissue maychange over time and/or in response to drug delivery, as describedabove, for example. In one embodiment, the band or clip may include asensing electrode. Sensors may be monitored and/or controlled viawireless telemetry, for example, thereby providing wireless monitoringof one or more tissue properties over time.

In one embodiment, one or more sensors may comprise a biosensor, forexample, comprising an immobilized biocatalyst, enzyme, immunoglobulin,bacterial, mammalian or plant tissue, cell and/or subcellular fractionof a cell. For example, the tip of a biosensor may comprise amitochondrial fraction of a cell, thereby providing the sensor with aspecific biocatalytic activity. In one embodiment, one or more sensorsmay be based on potentiometric technology or fiber optic technology. Forexample, a sensor may comprise a potentiometric or fiber optictransducer. An optical sensor may be based on either an absorbance orfluorescence measurement and may include an UV, a visible or an IR lightsource. In one embodiment, one or more sensors may be used to detectnaturally detectable properties representative of one or morecharacteristics, e.g., chemical, physical or physiological, of apatient's bodily tissues or fluids. For example, naturally detectableproperties of patient's bodily tissues or fluids may include pH, fluidflow, electrical current, impedance, temperature, pressure, componentsof metabolic processes, chemical concentrations, for example, theabsence or presence of specific peptides, proteins, enzymes, gases,ions, etc. In one embodiment, one or more sensors may include one ormore imaging systems, camera systems operating in UV, visible, or IRrange; electrical sensors; voltage sensors; current sensors;piezoelectric sensors; electromagnetic interference (EMI) sensors;photographic plates, polymer-metal sensors; charge-coupled devices(CCDs); photo diode arrays; chemical sensors, electrochemical sensors;pressure sensors, vibration sensors, sound wave sensors; magneticsensors; UV light sensors; visible light sensors; IR light sensors;radiation sensors; flow sensors; temperature sensors; or any otherappropriate or suitable sensor. In one embodiment, one or more sensorsmay be powered by a suitable power source. In addition, one or moresensors may be coupled to any appropriate output device, for example, aLCD or CRT monitor which receives and displays information regarding oneor more sensors.

A temperature sensor may incorporate one or more temperature-sensingelements such as, for example, thermocouples, thermisters,temperature-sensing liquid crystals, or temperature-sensing chemicals. Atemperature sensor could be used, for example, to monitor tissuetemperature.

The signals from one or more sensor may be amplified by a suitableamplifier before reaching an output device. The amplifier also may beincorporated into an output device. Alternatively, the amplifier may bea separate device. The output device may incorporate one or moreprocessors. In one embodiment, sensors may be positioned around aperimeter of the band or clip. When sensed tissue reaches a perimeter, acorresponding sensor may send a signal. In one embodiment, a sensor maysend constant signals. For example, a sensor may send a constant signalbased on its voltage. As a tissue perimeter changes, the voltage of thesensor may change proportionately and the signal sent by the sensor maychange proportionately.

FIGS. 74 and 75 illustrate one embodiment of device 200 for ligation ofan atrial appendage. In this embodiment, device 200 includes a ringapplicator or delivery tool 202 and an occlusion member or ring 214. Thedelivery tool 202 can include a ring spreader 240 having ring-expandingmembers 242 used to hold and expand the ring 214. The ring spreader 240can be coupled to a distal end of shaft 220. In one embodiment, thedelivery tool 202 can include three ring-expanding members 242. As shownin FIG. 76, the ring 214 can be releasably coupled or attached to thedistal end of ring-expanding members 242, for example, via wire hooks272 made of stainless steel or nitinol, for example. The wire hooks 272may be passed through one or more lumens 278 within ring-expandingmembers 242. The wire hooks 272 may be retracted partially (as shown inFIGS. 77 and 78) or completely into ring-expanding members 242 via aring release mechanism 273 located at the proximal end of device 20,thereby releasing ring 214 from delivery tool 202. The handle 230 mayalso include a ring expansion mechanism 260 used to control theexpansion of the ring 214. In one embodiment, ring expansion mechanism260 is coupled to a wedge member 274 via a shaft 275. As the wedgemember 274 is moved via ring expansion mechanism 260 from a distalposition to a more proximal position the ring expanding members 242 areforced to move from a closed or collapsed configuration to an open orexpanded configuration, as shown in FIGS. 74 and 75.

FIG. 79 illustrates one embodiment of device 200 for ligation of anatrial appendage. In this embodiment, device 200 includes a ringapplicator or delivery tool 202 and an occlusion member or ring 214. Thedelivery tool 202 can include a ring spreader 240 having ring-expandingmembers 242 used to hold and expand the ring 214. The ring spreader 240can be coupled to a distal end of shaft 220. In one embodiment, thedelivery tool 202 can include three ring-expanding members 242 pivotallycoupled to distal end of shaft 220, as shown in FIG. 80. As shown inFIG. 81, the ring 214 can be releasably coupled to the distal end ofring-expanding members 242, for example, via ring attachment members 252pivotally coupled to ring expanding members 242. In one embodiment, ringattachment members 252 may be remotely controlled to pivot therebyreleasing ring 214 from delivery tool 202. A ring release mechanism 273,coupled to ring attachment members 252, may be located at or near handle230. Ring release mechanism 273 may be used to control the pivoting ofring attachment members 252 thereby releasing ring 214 from deliverytool 202. The handle 230 may also include a ring expansion mechanism 260used to control the expansion of the ring 214. The ring expansionmechanism 260 may be coupled to the ring-expanding members 242. The ringexpansion mechanism 260 can control movement of the ring expandingmembers 242 from a closed or collapsed configuration to an open orexpanded configuration, as shown in FIGS. 79 and 80.

FIG. 82 illustrates one embodiment of device 34 for ligation of anatrial appendage, wherein ring applicator 34 includes a shaft 36 with ahandle 38 on a proximal end and a ring spreader 40 on a distal end. Inone embodiment, the ring spreader 40 includes a pair of spreader jaws 42and 44. In one embodiment, a spring member may bias the jaws into anopen or expanded configuration and/or a closed or collapsedconfiguration. In an alternative embodiment, the jaw arms 42 and 44 mayride on a cylinder 51 which forces the arms apart when they are pushedforward out the distal end of shaft 36. FIG. 83 shows one embodiment ofring spreader 40 in a closed or collapsed configuration. FIG. 84 showsone embodiment of ring spreader 40 in an open or expanded configuration.In one embodiment, a jaw actuator 48 is moveably coupled to handle 38.The jaw actuator 48 includes a shaft 49 connected to jaws 42 and 44.When the shaft 49 is pushed forward within the shaft 36, jaws 42 and 44are forced out the distal end of shaft 36 and into an open or expandedconfiguration. In some embodiments, as shown in FIG. 9B, the ring 16 canbe removably attached to the ring spreader 40 by one or more sutures,which may act as a retainer to hold the ring 16 in the ring spreader 40.

In some embodiments, the shaft of the ring, band or clip delivery toolmay comprise one or more flexible, bendable and/or articulation sectionand/or sections. One or more flexible, bendable and/or articulationsection and/or sections of the shaft of the delivery tool allows thedevice to accommodate a variety of patient anatomies via flexing,bending and/or articulation of the delivery tool's shaft. Preferably,any flexing, bending and/or articulation of the shaft will not inhibitthe opening and closing mechanism of the delivery tool for opening andclosing the ring, band or clip.

In one embodiment, as shown in FIG. 85, a portion of the shaft of thedelivery tool may comprise an outer tube member 110 made of a memoryalloy and/or plastic which may be pre-bent to a desired angle, forexample 90°. The shaft may then comprise an inner stiffening rod member111 placed within a lumen 112 of the outer tube member 110. The innerstiffening rod member 111 may be used to straighten the outer tube ifadvanced within the lumen 112 of the outer tube member 110 and allow theouter tube member 110 to return to its pre-bent shape if retracted. Inone embodiment, the stiffening rod member 111 may be controlled by arotating collar axially located with the outer tube member 110 andstiffening rod member 111. In one embodiment, the shaft or outer tubemember 10 may include one or more lumens for control lines thatfacilitate the opening and closing mechanism or ring spreader of thedelivery tool for opening and closing the ring, band or clip.

In one embodiment, as shown in FIGS. 86 and 87, a portion of the shaftof the delivery tool may comprise on or more hinge mechanisms 310, e.g.,a hinge mechanism comprising multiple living hinges along a shaftsection to create a gradual bend or curve for articulation. In oneembodiment, one or more lumens 311 for control lines that facilitate theopening and closing mechanism or ring spreader of the delivery tool maybe located as close to or through the pivots 312 of the hinges, therebyinsuring that the control lines would not substantially lengthen orshorten throughout the range of hinge articulation. A cable or rod maybe used, for example, to operate the hinge mechanism 310, therebyarticulating the shaft portion comprising the living hinges, forexample. One or more lumens 313 may be used for the cable or rod. Thearticulation of the hinge mechanism 310, e.g., the pushing and pullingof the cable or rod, may be controlled by a rotating collar axiallylocated with the shaft. A gradual bend curve formed from the multipleliving hinges prevents sharp bends or kinking in the opening and closingmechanism control lines, thereby insuring good working conditions forthe opening and closing mechanism.

FIG. 88 illustrates one embodiment of device 300 for ligation of anatrial appendage, wherein ring applicator 300 includes a shaft 36 with ahandle or hand piece 38 on a proximal end and a ring spreader 40 on adistal end. Shaft 36 may include an articulation section 320, forexample, located at the distal portion of shaft 36, see FIG. 89. In oneembodiment, articulation section 320 of shaft 36 may include one or morehinge mechanisms as shown in FIG. 90. In one embodiment, hinge mechanism325 includes multiple living hinges controlled via a hinge articulationcontrol wire 330. Moving control wire 330 in a proximal direction causesarticulation section 320 to form a bend or curve. Moving control wire330 in a distal direction causes articulation section 320 to straighten.In one embodiment, articulation control wire 330 is coupled to anarticulation actuator or drive mechanism 335 positioned at the distalend of handle or hand piece 38. In one embodiment, as shown in FIGS. 91,92 and 93, articulation drive mechanism 335 comprises an articulationdrive screw 340 and an articulation drive screw knob 345 used tomanually control the movement of control wire 330 in both a distaldirection and a proximal direction. Rotation of drive screw knob 345causes drive screw 340 to rotate, which, in turn, causes control wire330 to move distally or proximally, thereby causing the hinged section320 to bend or straighten.

In one embodiment, as shown in FIG. 90, ring spreader 40 includes a ringspreader drive wire 350 used to expand at least one embodiment of ring14. For example, ring 14 may include a textile or fabric mesh covering355 as shown in FIGS. 94 and 95. The fabric mesh covering 355 may coverthe entire ring 14. Spreader drive wire 350 may run through a meshcovering lumen 357 as shown in FIG. 95. In one embodiment, the distalend of spreader drive wire 350 is fixed in place within mesh coveringlumen 357 so that as drive wire 350 is pushed distally into meshcovering lumen 357 the mesh covering expands. Expansion of the meshcovering 355 forces ring 14 to expand. When drive wire 350 is pulledback proximally, the mesh and band contract back to a pre-expandedconfiguration. In one embodiment, the ring and mesh covering areexpanded via drive wire 350 and they are positioned on the left atrialappendage as desired. Drive wire 350 may then be pulled proximally outof the mesh, thereby causing the ring and mesh covering to contractaround the atrial appendage. In an alternative embodiment, the ring andmesh covering are expanded via drive wire 350 and they are positioned onthe left atrial appendage as desired. Drive wire 350 may then be pulledproximally, thereby causing the ring and mesh covering to contractaround the atrial appendage. The drive wire and mesh covering may thenbe removed completely from the ring, for example, via a suture orrunning stitch 356. The running stitch may be pulled out of the meshcovering thereby allowing the mesh covering to be removed from the ring.In one embodiment, as shown in FIG. 95, the running stitch may belocated along the mesh covering and along the inside lumen of ring 14.In some embodiments, drive wire 350 may be releasably coupled to ring 14via a mesh covering, one or more sutures, and/or one or more wires, forexample.

In one embodiment, as shown in FIGS. 96 and 97, ring spreader drive wire350 is coupled to a ring spreader actuator or drive mechanism 360positioned at the proximal end of handle or hand piece 38. In oneembodiment, ring spreader drive mechanism 360 comprises a hand triggermechanism 365 used to manually control the movement of ring spreaderdrive wire 350 in both a distal direction and a proximal direction,thereby controlling the expansion and contraction of ring 14. As shownin FIG. 97, ring spreader drive mechanism 360 may also comprise a drivewire release assembly 370. Drive wire release assembly 370 allows thering spreader drive wire 350 to be released from ring spreader drivemechanism 360. Drive wire release assembly 370 may comprise a spring372. Spring 372 may be used to provide a desired amount of force ortension on drive wire 350. Drive wire release assembly 370 may comprisea drive wire release member 374. In one embodiment, drive wire releasemember 374 includes a release mechanism that is designed to releasedrive wire 350 when it is squeezed. In one embodiment, drive wirerelease assembly 370 includes locking pins 375, drive shaft members 376and 377 and plunger 378 and plunger shaft 379. In one embodiment, asshown in FIGS. 98A, 98B and 98C, the drive wire release mechanism ofdrive wire release member 374 may comprise a coupler 380 coupled todrive wire 350 that when squeezed, opens a pair of jaws, which allowsthe user to pull the coupler free from the rest of the device.

Furthermore, other substitutions, modifications, changes, and omissionsmay be made in the design, operating conditions, and arrangements of theexemplary embodiments without departing from the scope of the inventionas expressed in the appended claims. In addition, it will be appreciatedby those skilled in the art that while the invention has been describedabove in connection with particular embodiments and examples, theinvention is not necessarily so limited, and that numerous otherembodiments, examples, uses, modifications and departures from theembodiments, examples and uses are intended to be encompassed by theclaims attached hereto. The entire disclosure of each patent andpublication cited herein is incorporated by reference, as if each suchpatent or publication were individually incorporated by referenceherein.

1. A system for occluding a left atrial appendage of a patient, thesystem comprising: a ring applicator including a shaft having a handleon a proximal end and a distal end, and a channel extending from thehandle to the distal end of the shaft, an actuator coupled to thehandle, and a ring spreader assembly on the distal end of the shaft, thering spreader assembly having a plurality of ring expanding members; anda ring occluder releasably attached to the plurality of ring expandingmembers, the ring occluder being stretched to an open position by theactuator to allow the ring occluder to be manipulated over tissue to beoccluded.
 2. The system of claim 1 wherein the actuator controls aposition of the plurality of ring expanding members.
 3. The system ofclaim 1 wherein the ring applicator includes a tissue-grasping member tomove a portion of the left atrial appendage and with respect to the ringoccluder.
 4. The system of claim 3 wherein the tissue-grasping memberincludes at least one of a hook, a barb, a grasper, an adhesive, and asuction device.
 5. The system of claim 3 wherein at least a portion ofthe tissue-grasping member is adapted to be movably positioned withinthe channel, the tissue-grasping member being moveable between a distalposition and a proximal position with respect to the shaft of the ringapplicator.
 6. The system of claim 1 wherein the ring occluder includesa tissue engagement surface.
 7. The system of claim 1 wherein the ringoccluder includes silicone rubber.
 8. The system of claim 1 wherein thering occluder is covered with a fabric material.
 9. The system of claim1 wherein the ring occluder includes at least one of micro-sized glassbeads, glass fibers, and metallic fibers.
 10. The system of claim 1wherein the ring occluder includes a biocompatible, elastomericmaterial.
 11. The system of claim 1 wherein the ring occluder includes adrug or pharmacological agent.
 12. The system of claim 1 wherein thering occluder includes one or more sensors.
 13. The system of claim 1wherein the shaft includes an articulation section.
 14. The system ofclaim 1 wherein the shaft includes one or more remotely controllablehinges.
 15. The system of claim 1 wherein the shaft is bendable.
 16. Thesystem of claim 1 wherein the shaft is flexible.
 17. A system foroccluding a left atrial appendage of a patient, the system comprising: aring applicator including a shaft having a handle on a proximal end anda distal end, an actuator coupled to the handle, and a ring spreaderassembly on the distal end of the shaft, the ring spreader assemblycoupled to the actuator and including a drive wire; and a ring occluderreleasably coupled to the drive wire, the ring occluder being stretchedto an open position by movement of the drive wire by the actuator toallow the ring occluder to be manipulated over tissue to be occluded.18. The system of claim 17 wherein the ring occluder includes a tissueengagement surface.
 19. The system of claim 17 wherein the ring occluderincludes silicone rubber.
 20. The system of claim 17 wherein the ringoccluder is covered with a fabric material.
 21. The system of claim 17wherein the ring occluder includes at least one of micro-sized glassbeads, glass fibers, and metallic fibers.
 22. The system of claim 17wherein the ring occluder includes a biocompatible, elastomericmaterial.
 23. The system of claim 17 wherein the ring occluder includesa drug or pharmacological agent.
 24. The system of claim 17 wherein thering occluder includes one or more sensors.
 25. The system of claim 17wherein the shaft includes an articulation section.
 26. The system ofclaim 17 wherein the shaft includes one or more remotely controllablehinges.
 27. The system of claim 17 wherein the shaft is bendable. 28.The system of claim 17 wherein the shaft is flexible.
 29. The system ofclaim 17 wherein the actuator includes a hand trigger.